Name: rs199823175
Published: September 21, 2022
License: Open Access

Welcome to the Reference SNP (rs) Report

All alleles are reported in the Forward orientation. Click on the Variant Details tab for details on Genomic Placement, Gene, and Amino Acid changes. HGVS names are in the HGVS tab.

Reference SNP (rs) Report

This page reports data for a single dbSNP Reference SNP variation (RefSNP or rs) from the new redesigned dbSNP build.
Top of the page reports a concise summary for the rs, with more specific details included in the corresponding tabs below.
All alleles are reported in the Forward orientation. Use the Genomic View to inspect the nucleotides flanking the variant, and its neighbors.
For more information see Help documentation.

rs199823175

Current Build 156

Released September 21, 2022

Organism: Homo sapiens
Position: chr2:44942213 (GRCh38.p14) Help
The anchor position for this RefSNP. Includes all nucleotides potentially affected by this change, thus it can differ from HGVS, which is right-shifted. See here for details.
Alleles: G>C / G>T
Variation Type: SNV Single Nucleotide Variation
Frequency: T=0.001292 (299/231504, GnomAD_exome)
T=0.002097 (292/139250, GnomAD)
T=0.000944 (110/116466, ExAC) (+ 4 more)
T=0.00206 (171/82864, ALFA)
T=0.00188 (20/10666, GO-ESP)
T=0.0005 (3/6404, 1000G_30x)
T=0.0004 (2/5008, 1000G)

Clinical Significance: Reported in ClinVar
Gene : Consequence: SIX3 : Missense Variant
SIX3-AS1 : 2KB Upstream Variant
Publications: 4 citations
Genomic View: See rs on genome

ALFA Allele Frequency
The ALFA project provide aggregate allele frequency from dbGaP. More information is available on the project page including descriptions, data access, and terms of use.

Release Version: 20230706150541

Population	Group	Sample Size	Ref Allele	Alt Allele
Total	Global	82986	G=0.99792	C=0.00000, T=0.00208
European	Sub	70246	G=0.99765	C=0.00000, T=0.00235
African	Sub	3516	G=1.0000	C=0.0000, T=0.0000
African Others	Sub	116	G=1.000	C=0.000, T=0.000
African American	Sub	3400	G=1.0000	C=0.0000, T=0.0000
Asian	Sub	3090	G=0.9994	C=0.0000, T=0.0006
East Asian	Sub	1896	G=1.0000	C=0.0000, T=0.0000
Other Asian	Sub	1194	G=0.9983	C=0.0000, T=0.0017
Latin American 1	Sub	146	G=1.000	C=0.000, T=0.000
Latin American 2	Sub	628	G=1.000	C=0.000, T=0.000
South Asian	Sub	104	G=1.000	C=0.000, T=0.000
Other	Sub	5256	G=0.9989	C=0.0000, T=0.0011

Frequency tab displays a table of the reference and alternate allele frequencies reported by various studies and populations. Table lines, where Population="Global" refer to the entire study population, whereas lines, where Group="Sub", refer to a study-specific population subgroupings (i.e. AFR, CAU, etc.), if available. Frequency for the alternate allele (Alt Allele) is a ratio of samples observed-to-total, where the numerator (observed samples) is the number of chromosomes in the study with the minor allele present (found in "Sample size", where Group="Sub"), and the denominator (total samples) is the total number of all chromosomes in the study for the variant (found in "Sample size", where Group="Study-wide" and Population="Global").

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Study	Population	Group	Sample Size	Ref Allele	Alt Allele
gnomAD - Exomes	Global	Study-wide	231504	G=0.998708	T=0.001292
gnomAD - Exomes	European	Sub	119118	G=0.998120	T=0.001880
gnomAD - Exomes	Asian	Sub	47820	G=1.00000	T=0.00000
gnomAD - Exomes	American	Sub	33966	G=0.99820	T=0.00180
gnomAD - Exomes	African	Sub	14872	G=0.99960	T=0.00040
gnomAD - Exomes	Ashkenazi Jewish	Sub	9888	G=0.9999	T=0.0001
gnomAD - Exomes	Other	Sub	5840	G=0.9988	T=0.0012
gnomAD - Genomes	Global	Study-wide	139250	G=0.997903	T=0.002097
gnomAD - Genomes	European	Sub	75234	G=0.99797	T=0.00203
gnomAD - Genomes	African	Sub	41888	G=0.99943	T=0.00057
gnomAD - Genomes	American	Sub	13566	G=0.99174	T=0.00826
gnomAD - Genomes	Ashkenazi Jewish	Sub	3314	G=0.9997	T=0.0003
gnomAD - Genomes	East Asian	Sub	3120	G=1.0000	T=0.0000
gnomAD - Genomes	Other	Sub	2128	G=0.9991	T=0.0009
ExAC	Global	Study-wide	116466	G=0.999056	T=0.000944
ExAC	Europe	Sub	70346	G=0.99856	T=0.00144
ExAC	Asian	Sub	24712	G=1.00000	T=0.00000
ExAC	American	Sub	11404	G=0.99947	T=0.00053
ExAC	African	Sub	9136	G=0.9997	T=0.0003
ExAC	Other	Sub	868	G=1.000	T=0.000
Allele Frequency Aggregator	Total	Global	82864	G=0.99794	C=0.00000, T=0.00206
Allele Frequency Aggregator	European	Sub	70142	G=0.99768	C=0.00000, T=0.00232
Allele Frequency Aggregator	Other	Sub	5252	G=0.9989	C=0.0000, T=0.0011
Allele Frequency Aggregator	African	Sub	3502	G=1.0000	C=0.0000, T=0.0000
Allele Frequency Aggregator	Asian	Sub	3090	G=0.9994	C=0.0000, T=0.0006
Allele Frequency Aggregator	Latin American 2	Sub	628	G=1.000	C=0.000, T=0.000
Allele Frequency Aggregator	Latin American 1	Sub	146	G=1.000	C=0.000, T=0.000
Allele Frequency Aggregator	South Asian	Sub	104	G=1.000	C=0.000, T=0.000
GO Exome Sequencing Project	Global	Study-wide	10666	G=0.99812	T=0.00188
GO Exome Sequencing Project	European American	Sub	7330	G=0.9975	T=0.0025
GO Exome Sequencing Project	African American	Sub	3336	G=0.9994	T=0.0006
1000Genomes_30x	Global	Study-wide	6404	G=0.9995	T=0.0005
1000Genomes_30x	African	Sub	1786	G=1.0000	T=0.0000
1000Genomes_30x	Europe	Sub	1266	G=0.9992	T=0.0008
1000Genomes_30x	South Asian	Sub	1202	G=1.0000	T=0.0000
1000Genomes_30x	East Asian	Sub	1170	G=1.0000	T=0.0000
1000Genomes_30x	American	Sub	980	G=0.998	T=0.002
1000Genomes	Global	Study-wide	5008	G=0.9996	T=0.0004
1000Genomes	African	Sub	1322	G=1.0000	T=0.0000
1000Genomes	East Asian	Sub	1008	G=1.0000	T=0.0000
1000Genomes	Europe	Sub	1006	G=0.9990	T=0.0010
1000Genomes	South Asian	Sub	978	G=1.000	T=0.000
1000Genomes	American	Sub	694	G=0.999	T=0.001

Variant Details tab shows known variant placements on genomic sequences: chromosomes (NC_), RefSeqGene, pseudogenes or genomic regions (NG_), and in a separate table: on transcripts (NM_) and protein sequences (NP_). The corresponding transcript and protein locations are listed in adjacent lines, along with molecular consequences from Sequence Ontology. When no protein placement is available, only the transcript is listed. Column "Codon[Amino acid]" shows the actual base change in the format of "Reference > Alternate" allele, including the nucleotide codon change in transcripts, and the amino acid change in proteins, respectively, allowing for known ribosomal slippage sites. To view nucleotides adjacent to the variant use the Genomic View at the bottom of the page - zoom into the sequence until the nucleotides around the variant become visible.

Genomic Placements

Sequence name	Change
GRCh38.p14 chr 2	NC_000002.12:g.44942213G>C
GRCh38.p14 chr 2	NC_000002.12:g.44942213G>T
GRCh37.p13 chr 2	NC_000002.11:g.45169352G>C
GRCh37.p13 chr 2	NC_000002.11:g.45169352G>T
SIX3 RefSeqGene	NG_016222.1:g.5316G>C
SIX3 RefSeqGene	NG_016222.1:g.5316G>T

Gene: SIX3, SIX homeobox 3 (plus strand)

Molecule type	Change	Amino acid[Codon]	SO Term
SIX3 transcript	NM_005413.4:c.109G>C	G [GGT] > R [CGT]	Coding Sequence Variant
homeobox protein SIX3	NP_005404.1:p.Gly37Arg	G (Gly) > R (Arg)	Missense Variant
SIX3 transcript	NM_005413.4:c.109G>T	G [GGT] > C [TGT]	Coding Sequence Variant
homeobox protein SIX3	NP_005404.1:p.Gly37Cys	G (Gly) > C (Cys)	Missense Variant

Gene: SIX3-AS1, SIX3 antisense RNA 1 (minus strand) : 2KB Upstream Variant

Molecule type	Change	Amino acid[Codon]	SO Term
SIX3-AS1 transcript variant 1	NR_103785.1:n.	N/A	Upstream Transcript Variant
SIX3-AS1 transcript variant 2	NR_103786.1:n.	N/A	Upstream Transcript Variant

Clinical Significance tab shows a list of clinical significance entries from ClinVar associated with the variation, per allele. Click on the RCV accession (i.e. RCV000001615.2) or Allele ID (i.e. 12274) to access full ClinVar report.

Allele: T (allele ID: 39338 )

ClinVar Accession	Disease Names	Clinical Significance
RCV000023330.8	Holoprosencephaly 2	Benign
RCV000023331.5	Schizencephaly	Pathogenic
RCV000171135.1	Solitary median maxillary central incisor syndrome	Pathogenic
RCV000173372.5	not specified	Likely-Benign
RCV000713302.5	not provided	Benign-Likely-Benign

Aliases tab displays HGVS names representing the variant placements and allele changes on genomic, transcript and protein sequences, per allele. HGVS name is an expression for reporting sequence accession and version, sequence type, position, and allele change. The column "Note" can have two values: "diff" means that there is a difference between the reference allele (variation interval) at the placement reported in HGVS name and the reference alleles reported in other HGVS names, and "rev" means that the sequence of this variation interval at the placement reported in HGVS name is in reverse orientation to the sequence(s) of this variation in other HGVS names not labeled as "rev".

Placement	G=	C	T
GRCh38.p14 chr 2	NC_000002.12:g.44942213=	NC_000002.12:g.44942213G>C	NC_000002.12:g.44942213G>T
GRCh37.p13 chr 2	NC_000002.11:g.45169352=	NC_000002.11:g.45169352G>C	NC_000002.11:g.45169352G>T
SIX3 RefSeqGene	NG_016222.1:g.5316=	NG_016222.1:g.5316G>C	NG_016222.1:g.5316G>T
SIX3 transcript	NM_005413.4:c.109=	NM_005413.4:c.109G>C	NM_005413.4:c.109G>T
SIX3 transcript	NM_005413.3:c.109=	NM_005413.3:c.109G>C	NM_005413.3:c.109G>T
homeobox protein SIX3	NP_005404.1:p.Gly37=	NP_005404.1:p.Gly37Arg	NP_005404.1:p.Gly37Cys

Submissions tab displays variations originally submitted to dbSNP, now supporting this RefSNP cluster (rs). We display Submitter handle, Submission identifier, Date and Build number, when the submission appeared for the first time. Direct submissions to dbSNP have Submission ID in the form of an ss-prefixed number (ss#). Other supporting variations are listed in the table without ss#.

43 SubSNP, 9 Frequency, 5 ClinVar submissions

No	Submitter	Submission ID	Date (Build)
1	EXOME_CHIP	ss491318468	May 04, 2012 (137)
2	NHLBI-ESP	ss712412287	Apr 25, 2013 (138)
3	ILLUMINA	ss780777062	Sep 08, 2015 (146)
4	ILLUMINA	ss783457070	Sep 08, 2015 (146)
5	OMIM-CURATED-RECORDS	ss825077463	Jun 20, 2013 (137)
6	1000GENOMES	ss1296967549	Aug 21, 2014 (142)
7	EVA_DECODE	ss1586172602	Apr 01, 2015 (144)
8	EVA_EXAC	ss1686292764	Apr 01, 2015 (144)
9	ILLUMINA	ss1752357966	Sep 08, 2015 (146)
10	ILLUMINA	ss1917748826	Feb 12, 2016 (147)
11	ILLUMINA	ss1946039181	Feb 12, 2016 (147)
12	ILLUMINA	ss1958413045	Feb 12, 2016 (147)
13	JJLAB	ss2020532064	Sep 14, 2016 (149)
14	GNOMAD	ss2732641607	Nov 08, 2017 (151)
15	GNOMAD	ss2746673114	Nov 08, 2017 (151)
16	GNOMAD	ss2772709896	Nov 08, 2017 (151)
17	AFFY	ss2985166923	Nov 08, 2017 (151)
18	SWEGEN	ss2989401343	Nov 08, 2017 (151)
19	ILLUMINA	ss3021965922	Nov 08, 2017 (151)
20	ILLUMINA	ss3628050042	Oct 11, 2018 (152)
21	ILLUMINA	ss3634763541	Oct 11, 2018 (152)
22	ILLUMINA	ss3640470843	Oct 11, 2018 (152)
23	ILLUMINA	ss3644741908	Oct 11, 2018 (152)
24	ILLUMINA	ss3652397351	Oct 11, 2018 (152)
25	ILLUMINA	ss3653937432	Oct 11, 2018 (152)
26	EVA_DECODE	ss3703763150	Jul 13, 2019 (153)
27	ILLUMINA	ss3725780416	Jul 13, 2019 (153)
28	ILLUMINA	ss3744474801	Jul 13, 2019 (153)
29	ILLUMINA	ss3745063453	Jul 13, 2019 (153)
30	ILLUMINA	ss3772560292	Jul 13, 2019 (153)
31	EVA	ss3823766379	Apr 25, 2020 (154)
32	EVA	ss3826951636	Apr 25, 2020 (154)
33	TOPMED	ss4503304300	Apr 26, 2021 (155)
34	TOPMED	ss4503304301	Apr 26, 2021 (155)
35	1000G_HIGH_COVERAGE	ss5247829789	Oct 12, 2022 (156)
36	EVA	ss5328498054	Oct 12, 2022 (156)
37	HUGCELL_USP	ss5448054030	Oct 12, 2022 (156)
38	1000G_HIGH_COVERAGE	ss5522919241	Oct 12, 2022 (156)
39	EVA	ss5820009686	Oct 12, 2022 (156)
40	EVA	ss5848513347	Oct 12, 2022 (156)
41	EVA	ss5930091125	Oct 12, 2022 (156)
42	EVA	ss5954830871	Oct 12, 2022 (156)
43	EVA	ss5979564797	Oct 12, 2022 (156)
44	1000Genomes	NC_000002.11 - 45169352	Oct 11, 2018 (152)
45	1000Genomes_30x	NC_000002.12 - 44942213	Oct 12, 2022 (156)
46	ExAC	NC_000002.11 - 45169352	Oct 11, 2018 (152)
47	gnomAD - Genomes	NC_000002.12 - 44942213	Apr 26, 2021 (155)
48	gnomAD - Exomes	NC_000002.11 - 45169352	Jul 13, 2019 (153)
49	GO Exome Sequencing Project	NC_000002.11 - 45169352	Oct 11, 2018 (152)
50	TopMed Submission ignored due to conflicting rows: Row 307127179 (NC_000002.12:44942212:G:C 1/264690) Row 307127180 (NC_000002.12:44942212:G:T 572/264690)	-	Apr 26, 2021 (155)
51	TopMed Submission ignored due to conflicting rows: Row 307127179 (NC_000002.12:44942212:G:C 1/264690) Row 307127180 (NC_000002.12:44942212:G:T 572/264690)	-	Apr 26, 2021 (155)
52	ALFA	NC_000002.12 - 44942213	Apr 26, 2021 (155)
53	ClinVar	RCV000023330.8	Oct 12, 2022 (156)
54	ClinVar	RCV000023331.5	Jul 13, 2019 (153)
55	ClinVar	RCV000171135.1	Oct 11, 2018 (152)
56	ClinVar	RCV000173372.5	Oct 12, 2022 (156)
57	ClinVar	RCV000713302.5	Oct 12, 2022 (156)

History tab displays RefSNPs (Associated ID) from previous builds (Build) that now support the current RefSNP, and the dates, when the history was updated for each Associated ID (History Updated).

Added to this RefSNP Cluster:

Submission IDs	Observation SPDI	Canonical SPDI	Source RSIDs
12666645214, ss4503304300	NC_000002.12:44942212:G:C	NC_000002.12:44942212:G:C	(self)
ss1586172602	NC_000002.10:45022855:G:T	NC_000002.12:44942212:G:T	(self)
7904126, 6161840, 1689317, 224845, ss491318468, ss712412287, ss780777062, ss783457070, ss1296967549, ss1686292764, ss1752357966, ss1917748826, ss1946039181, ss1958413045, ss2020532064, ss2732641607, ss2746673114, ss2772709896, ss2985166923, ss2989401343, ss3021965922, ss3628050042, ss3634763541, ss3640470843, ss3644741908, ss3652397351, ss3653937432, ss3744474801, ss3745063453, ss3772560292, ss3823766379, ss3826951636, ss5328498054, ss5820009686, ss5848513347, ss5954830871, ss5979564797	NC_000002.11:45169351:G:T	NC_000002.12:44942212:G:T	(self)
RCV000023330.8, RCV000023331.5, RCV000171135.1, RCV000173372.5, RCV000713302.5, 10445176, 56106304, 12666645214, ss825077463, ss3703763150, ss3725780416, ss4503304301, ss5247829789, ss5448054030, ss5522919241, ss5930091125	NC_000002.12:44942212:G:T	NC_000002.12:44942212:G:T	(self)

Publications tab displays PubMed articles citing the variation as a listing of PMID, Title, Author, Year, Journal, ordered by Year, descending.

4 citations for rs199823175

PMID	Title	Author	Year	Journal
18791198	Mutations in the human SIX3 gene in holoprosencephaly are loss of function.	Domené S et al.	2008	Human molecular genetics
19346217	Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function.	Lacbawan F et al.	2009	Journal of medical genetics
20157829	Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly.	Hehr U et al.	2010	Human genetics
26080100	Genotypic and phenotypic variation in six patients with solitary median maxillary central incisor syndrome.	Poelmans S et al.	2015	American journal of medical genetics. Part A

The Flanks tab provides retrieving flanking sequences of a SNP on all molecules that have placements.

Genome context:

Select flank length:

Genomic regions, transcripts, and products
Top▲ Help
NCBI Graphical Sequence Viewer display of the genomic region, transcripts and protein products for the reported RefSNP (rs).
Use the zoom option to view the nucleotides around the RefSNP and find other neighboring RefSNPs.
Visit Sequence Viewer for help with navigating inside the display and modifying the selection of displayed data tracks.

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dbSNP Short Genetic Variations

Welcome to the Reference SNP (rs) Report

Reference SNP (rs) Report

rs199823175