NM_001953.5(TYMP):c.389C>T (p.Ala130Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 10, 2022
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:: RCV003072020.3

Allele description [Variation Report for NM_001953.5(TYMP):c.389C>T (p.Ala130Val)]

NM_001953.5(TYMP):c.389C>T (p.Ala130Val)

Gene:

TYMP:thymidine phosphorylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_001953.5(TYMP):c.389C>T (p.Ala130Val)

HGVS:

NC_000022.11:g.50529164G>A
NG_011860.1:g.5922C>T
NG_016235.1:g.2276C>T
NM_001113755.3:c.389C>T
NM_001113756.3:c.389C>T
NM_001257988.1:c.389C>T
NM_001257989.1:c.389C>T
NM_001953.3:c.389C>T
NM_001953.5:c.389C>TMANE SELECT
NP_001107227.1:p.Ala130Val
NP_001107228.1:p.Ala130Val
NP_001244917.1:p.Ala130Val
NP_001244918.1:p.Ala130Val
NP_001944.1:p.Ala130Val
LRG_727t1:c.389C>T
LRG_727t2:c.389C>T
LRG_727:g.5922C>T
LRG_727p1:p.Ala130Val
LRG_727p2:p.Ala130Val
NC_000022.10:g.50967593G>A

Protein change:

A130V

Molecular consequence:

NM_001113755.3:c.389C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001113756.3:c.389C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257988.1:c.389C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257989.1:c.389C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001953.5:c.389C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Scn5a sodium channel, voltage-gated, type V, alpha [Mus musculus]
Scn5a sodium channel, voltage-gated, type V, alpha [Mus musculus]
Gene ID:20271

Gene
20271[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003460305	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 28, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003803172	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003460305

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 28, 2022)

germline

clinical testing

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

SCV003803172

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 10, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003460305.1

#	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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 130 of the TYMP protein (p.Ala130Val). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TYMP-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TYMP protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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

From GeneDx, SCV003803172.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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

Last Updated: Sep 29, 2024

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