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NM_000479.5(AMH):c.35T>G (p.Val12Gly) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 27, 2023
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:
RCV000439837.6

Allele description [Variation Report for NM_000479.5(AMH):c.35T>G (p.Val12Gly)]

NM_000479.5(AMH):c.35T>G (p.Val12Gly)

Genes:
LOC108783649:AMH 5' regulatory region [Gene]
AMH:anti-Mullerian hormone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_000479.5(AMH):c.35T>G (p.Val12Gly)
HGVS:
  • NC_000019.10:g.2249367T>G
  • NG_012190.1:g.5254T>G
  • NG_051647.1:g.3134T>G
  • NM_000479.4:c.35T>G
  • NM_000479.5:c.35T>GMANE SELECT
  • NP_000470.3:p.Val12Gly
  • NC_000019.9:g.2249366T>G
  • NM_000479.3:c.35T>G
Protein change:
V12G
Links:
dbSNP: rs149082963
NCBI 1000 Genomes Browser:
rs149082963
Molecular consequence:
  • NM_000479.5:c.35T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000521317GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(May 5, 2016) 		germlineclinical testing

Citation Link,

SCV002193653Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 27, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular genetics of the persistent müllerian duct syndrome: a study of 19 families.

Imbeaud S, Carré-Eusèbe D, Rey R, Belville C, Josso N, Picard JY.

Hum Mol Genet. 1994 Jan;3(1):125-31.

PubMed [citation]
PMID:
8162013

AMH gene mutations in two Egyptian families with persistent müllerian duct syndrome.

Mazen I, Abdel Hamid MS, El-Gammal M, Aref A, Amr K.

Sex Dev. 2011;5(6):277-80. doi: 10.1159/000334854. Epub 2011 Dec 20.

PubMed [citation]
PMID:
22188863
See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000521317.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The V12G variant in the AMH gene has been reported previously in persistent Müllerian duct syndrome, in an affected individual who was compound heterozygous for the V12G variant and another AMH variant (Imbeaud et al., 1994). The NHLBI ESP Exome Sequencing Project reports V12G was observed in 0.28%, 24/8572 alleles, although not in the homozygous state, from individuals of European background, indicating it may be a rare variant in this population. The V12G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V12G as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002193653.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 12 of the AMH protein (p.Val12Gly). This variant is present in population databases (rs149082963, gnomAD 0.3%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of persistent Müllerian Duct Syndrome (PMID: 8162013, 22188863). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 381731). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Studies have shown that this missense change does not affect mRNA splicing (PMID: 37004205). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024