NM_058179.4(PSAT1):c.386G>A (p.Gly129Glu) AND Neu-Laxova syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV001879910.4

Allele description [Variation Report for NM_058179.4(PSAT1):c.386G>A (p.Gly129Glu)]

NM_058179.4(PSAT1):c.386G>A (p.Gly129Glu)

Gene:

PSAT1:phosphoserine aminotransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q21.2

Genomic location:

Preferred name:

NM_058179.4(PSAT1):c.386G>A (p.Gly129Glu)

HGVS:

NC_000009.12:g.78304929G>A
NG_012165.1:g.12787G>A
NM_021154.5:c.386G>A
NM_058179.4:c.386G>AMANE SELECT
NP_066977.1:p.Gly129Glu
NP_478059.1:p.Gly129Glu
NC_000009.11:g.80919845G>A
NC_000009.11:g.80919845G>A

Protein change:

G129E

Links:

dbSNP: rs368015309

NCBI 1000 Genomes Browser:

rs368015309

Molecular consequence:

NM_021154.5:c.386G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_058179.4:c.386G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

function_uncertain_variant [Sequence Ontology: SO:0002220] - Comment(s)
- Impaired relative to wildtype, but less than all known disease alleles. PMID:32077105 Table S7.
mutation affecting coding sequence [Sequence Ontology: SO:1000054] - Comment(s)
- Impaired relative to wildtype, but less than all known disease alleles. PMID:32077105 Table S7.

Condition(s)

Name:: Neu-Laxova syndrome 2
Identifiers:: MONDO: MONDO:0014466; MedGen: C4015019; Orphanet: 2671; OMIM: 616038

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002191091	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32077105, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002191091

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 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

A yeast-based complementation assay elucidates the functional impact of 200 missense variants in human PSAT1.

Sirr A, Lo RS, Cromie GA, Scott AC, Ashmead J, Heyesus M, Dudley AM.

J Inherit Metab Dis. 2020 Jul;43(4):758-769. doi: 10.1002/jimd.12227. Epub 2020 Feb 27.

PubMed [citation]

PMID:: 32077105
PMCID:: PMC7444316

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, SCV002191091.3

#	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 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. Experimental studies have shown that this missense change does not substantially affect PSAT1 function (PMID: 32077105). 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 not expected to disrupt PSAT1 protein function. ClinVar contains an entry for this variant (Variation ID: 977037). This variant has not been reported in the literature in individuals affected with PSAT1-related conditions. This variant is present in population databases (rs368015309, gnomAD 0.006%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 129 of the PSAT1 protein (p.Gly129Glu).

#	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: Sep 29, 2024

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