NM_058179.4(PSAT1):c.338A>T (p.Glu113Val) AND Neu-Laxova syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 2022
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:: RCV001879900.6

Allele description [Variation Report for NM_058179.4(PSAT1):c.338A>T (p.Glu113Val)]

NM_058179.4(PSAT1):c.338A>T (p.Glu113Val)

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.338A>T (p.Glu113Val)

HGVS:

NC_000009.12:g.78304881A>T
NG_012165.1:g.12739A>T
NM_021154.5:c.338A>T
NM_058179.4:c.338A>TMANE SELECT
NP_066977.1:p.Glu113Val
NP_478059.1:p.Glu113Val
NC_000009.11:g.80919797A>T
NC_000009.11:g.80919797A>T

Protein change:

E113V

Links:

dbSNP: rs373888510

NCBI 1000 Genomes Browser:

rs373888510

Molecular consequence:

NM_021154.5:c.338A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_058179.4:c.338A>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functionally_normal [Sequence Ontology: SO:0002219] - Comment(s)
- Not impaired relative to wildtype. PMID:32077105 Table S7.
mutation affecting coding sequence [Sequence Ontology: SO:1000054] - Comment(s)
- Not impaired relative to wildtype. 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
SCV002169076	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2022)	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

SCV002169076

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2022)

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, SCV002169076.3

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 976985). This variant has not been reported in the literature in individuals affected with PSAT1-related conditions. This variant is present in population databases (rs373888510, gnomAD 0.02%). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 113 of the PSAT1 protein (p.Glu113Val). Experimental studies have shown that this missense change does not substantially affect PSAT1 function (PMID: 32077105). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

#	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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