NM_001002010.5(NT5C3A):c.395A>T (p.Asp132Val) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 29, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003555917.1

Allele description [Variation Report for NM_001002010.5(NT5C3A):c.395A>T (p.Asp132Val)]

NM_001002010.5(NT5C3A):c.395A>T (p.Asp132Val)

Gene:

NT5C3A:5'-nucleotidase, cytosolic IIIA [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p14.3

Genomic location:

Preferred name:

NM_001002010.5(NT5C3A):c.395A>T (p.Asp132Val)

HGVS:

NC_000007.14:g.33021317T>A
NG_015800.1:g.46481A>T
NM_001002009.3:c.293A>T
NM_001002010.5:c.395A>TMANE SELECT
NM_001166118.3:c.257A>T
NM_001356996.3:c.257A>T
NM_001374335.1:c.296A>T
NM_001374336.1:c.257A>T
NM_001374337.1:c.257A>T
NM_001374338.1:c.395A>T
NM_001374339.1:c.194A>T
NM_016489.14:c.293A>T
NP_001002009.1:p.Asp98Val
NP_001002010.2:p.Asp132Val
NP_001159590.1:p.Asp86Val
NP_001343925.1:p.Asp86Val
NP_001361264.1:p.Asp99Val
NP_001361265.1:p.Asp86Val
NP_001361266.1:p.Asp86Val
NP_001361267.1:p.Asp132Val
NP_001361268.1:p.Asp65Val
NP_057573.2:p.Asp98Val
NC_000007.13:g.33060929T>A
Q9H0P0:p.Asp137Val

Protein change:

D132V; ASP98VAL

Links:

UniProtKB: Q9H0P0#VAR_023511; OMIM: 606224.0001; dbSNP: rs104894025

NCBI 1000 Genomes Browser:

rs104894025

Molecular consequence:

NM_001002009.3:c.293A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001002010.5:c.395A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001166118.3:c.257A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001356996.3:c.257A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374335.1:c.296A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374336.1:c.257A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374337.1:c.257A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374338.1:c.395A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374339.1:c.194A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_016489.14:c.293A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295106	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 29, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11369620, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295106

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 29, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Genetic basis of hemolytic anemia caused by pyrimidine 5' nucleotidase deficiency.

Marinaki AM, Escuredo E, Duley JA, Simmonds HA, Amici A, Naponelli V, Magni G, Seip M, Ben-Bassat I, Harley EH, Thein SL, Rees DC.

Blood. 2001 Jun 1;97(11):3327-32.

PubMed [citation]

PMID:: 11369620

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 Invitae, SCV004295106.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 NT5C3A protein function. ClinVar contains an entry for this variant (Variation ID: 4479). This missense change has been observed in individuals with pyrimidine 5'-nucleotidase deficiency (PMID: 11369620; Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs104894025, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 98 of the NT5C3A protein (p.Asp98Val).

#	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: Feb 20, 2024

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Relating variation to medicine