NM_012082.4(ZFPM2):c.442A>G (p.Met148Val) AND 46,XY sex reversal 9

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 26, 2021
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:: RCV001890492.6

Allele description

NM_012082.4(ZFPM2):c.442A>G (p.Met148Val)

Gene:

ZFPM2:zinc finger protein, FOG family member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q23.1

Genomic location:

Preferred name:

NM_012082.4(ZFPM2):c.442A>G (p.Met148Val)

HGVS:

NC_000008.11:g.105634267A>G
NG_011723.2:g.320349A>G
NM_001362836.2:c.283A>G
NM_001362837.2:c.46A>G
NM_012082.4:c.442A>GMANE SELECT
NP_001349765.1:p.Met95Val
NP_001349766.1:p.Met16Val
NP_036214.2:p.Met148Val
NC_000008.10:g.106646495A>G

Protein change:

M148V

Links:

dbSNP: rs370456245

NCBI 1000 Genomes Browser:

rs370456245

Molecular consequence:

NM_001362836.2:c.283A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001362837.2:c.46A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_012082.4:c.442A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: 46,XY sex reversal 9 (SRXY9)
Synonyms:: 46,XY SEX REVERSAL, ZFPM2-RELATED
Identifiers:: MONDO: MONDO:0014480; MedGen: C4015129; Orphanet: 251510; OMIM: 616067

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002151023	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 26, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28166811, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002151023

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 26, 2021)

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

Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.

Genome Med. 2017 Feb 6;9(1):13. doi: 10.1186/s13073-017-0403-7.

PubMed [citation]

PMID:: 28166811
PMCID:: PMC5295186

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, SCV002151023.3

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ZFPM2-related conditions. This variant is present in population databases (rs370456245, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This sequence change replaces methionine with valine at codon 148 of the ZFPM2 protein (p.Met148Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine.

#	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: Aug 4, 2024

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