VCV001341777.23 - ClinVar

NM_001348323.3(TRIP12):c.748G>A (p.Ala250Thr)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(2)

3 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001348323.3(TRIP12):c.748G>A (p.Ala250Thr)

Variation ID: 1341777 Accession: VCV001341777.23

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q36.3 2: 229859051 (GRCh38) [ NCBI UCSC ] 2: 230723767 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 20, 2022	Jan 11, 2026	May 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001348323.3:c.748G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001335252.1:p.Ala250Thr	missense
NM_001284214.2:c.748G>A	NP_001271143.1:p.Ala250Thr	missense
NM_001284215.2:c.622G>A	NP_001271144.1:p.Ala208Thr	missense
NM_001284216.2:c.98+20931G>A		intron variant
NM_001348315.2:c.748G>A	NP_001335244.1:p.Ala250Thr	missense
NM_001348316.2:c.622G>A	NP_001335245.1:p.Ala208Thr	missense
NM_001348317.1:c.622G>A	NP_001335246.1:p.Ala208Thr	missense
NM_001348318.2:c.622G>A	NP_001335247.1:p.Ala208Thr	missense
NM_001348319.1:c.748G>A	NP_001335248.1:p.Ala250Thr	missense
NM_001348320.2:c.748G>A	NP_001335249.1:p.Ala250Thr	missense
NM_001348321.1:c.748G>A	NP_001335250.1:p.Ala250Thr	missense
NM_001348322.1:c.748G>A	NP_001335251.1:p.Ala250Thr	missense
NM_001348324.2:c.748G>A	NP_001335253.1:p.Ala250Thr	missense
NM_001348325.2:c.748G>A	NP_001335254.1:p.Ala250Thr	missense
NM_001348326.2:c.748G>A	NP_001335255.1:p.Ala250Thr	missense
NM_001348327.2:c.748G>A	NP_001335256.1:p.Ala250Thr	missense
NM_001348328.1:c.748G>A	NP_001335257.1:p.Ala250Thr	missense
NM_001348329.2:c.748G>A	NP_001335258.1:p.Ala250Thr	missense
NM_001348330.2:c.748G>A	NP_001335259.1:p.Ala250Thr	missense
NM_001348331.1:c.622G>A	NP_001335260.1:p.Ala208Thr	missense
NM_001348332.1:c.748G>A	NP_001335261.1:p.Ala250Thr	missense
NM_001348333.1:c.748G>A	NP_001335262.1:p.Ala250Thr	missense
NM_001348334.1:c.748G>A	NP_001335263.1:p.Ala250Thr	missense
NM_001348335.2:c.748G>A	NP_001335264.1:p.Ala250Thr	missense
NM_001348336.1:c.748G>A	NP_001335265.1:p.Ala250Thr	missense
NM_004238.1:c.622G>A
NM_004238.3:c.622G>A	NP_004229.1:p.Ala208Thr	missense
NC_000002.12:g.229859051C>T
NC_000002.11:g.230723767C>T
NG_053017.1:g.69184G>A

... more HGVS ... less HGVS

Protein change

A208T, A250T

Other names

Canonical SPDI

NC_000002.12:229859050:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD) 0.00004

Exome Aggregation Consortium (ExAC) 0.00013

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA2153455 dbSNP: rs539119124 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TRIP12		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	690	755

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Clark-Baraitser syndrome	Uncertain significance (1)	criteria provided, single submitter	Jan 15, 2021	RCV001837257.1
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	May 30, 2022	RCV002542800.2
not provided	Likely benign (1)	criteria provided, single submitter	May 1, 2023	RCV003434329.20

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Jan 15, 2021) C Contributing to aggregate classification	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Clark-Baraitser syndrome	New York Genome Center Study: CSER-NYCKidSeq Accession: SCV002097770.1 First in ClinVar: Feb 20, 2022 Last updated: Feb 20, 2022	Observation: 1 Collection method: clinical testing Allele origin: inherited Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: inherited Affected status: unknown Clinical Features: Intellectual disability (present) , Autism (present) Test name: whole genome sequencing Zygosity: 1 Single Heterozygote Secondary finding: no Platform name: NovaSeq 6000

Likely benign (May 30, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV003710185.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (May 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV004151584.20 First in ClinVar: Nov 20, 2023 Last updated: Jan 11, 2026	Comment: show TRIP12: PP2, BP4, BS1 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs539119124 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 11, 2026