NM_001378454.1(ALMS1):c.10862A>G (p.Lys3621Arg) AND Alstrom syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 15, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000669081.2

Allele description [Variation Report for NM_001378454.1(ALMS1):c.10862A>G (p.Lys3621Arg)]

NM_001378454.1(ALMS1):c.10862A>G (p.Lys3621Arg)

Gene:

ALMS1:ALMS1 centrosome and basal body associated protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_001378454.1(ALMS1):c.10862A>G (p.Lys3621Arg)

HGVS:

NC_000002.12:g.73572739A>G
NG_011690.1:g.191987A>G
NM_001378454.1:c.10862A>GMANE SELECT
NM_015120.4:c.10865A>G
NP_001365383.1:p.Lys3621Arg
NP_055935.4:p.Lys3622Arg
LRG_741t1:c.10865A>G
LRG_741:g.191987A>G
LRG_741p1:p.Lys3622Arg
NC_000002.11:g.73799866A>G

Protein change:

K3621R

Links:

dbSNP: rs1288339942

NCBI 1000 Genomes Browser:

rs1288339942

Molecular consequence:

NM_001378454.1:c.10862A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015120.4:c.10865A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Alstrom syndrome (ALMS)
Synonyms:: Alstrom's syndrome
Identifiers:: MONDO: MONDO:0008763; MedGen: C0268425; Orphanet: 64; OMIM: 203800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793784	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Aug 30, 2017)	unknown	clinical testing	Citation Link,
SCV003504595	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793784

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Aug 30, 2017)

unknown

clinical testing

Citation Link,

SCV003504595

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 15, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Counsyl, SCV000793784.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV003504595.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces lysine with arginine at codon 3622 of the ALMS1 protein (p.Lys3622Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 553600). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 28, 2023

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