chr19-2249605-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000479.5(AMH):c.273C>T(p.Arg91=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000801 in 1,548,068 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00014 ( 1 hom., cov: 34)
Exomes 𝑓: 0.000074 ( 0 hom. )
Consequence
AMH
NM_000479.5 synonymous
NM_000479.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0180
Genes affected
AMH (HGNC:464): (anti-Mullerian hormone) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate N- and C-terminal cleavage products that homodimerize and associate to form a biologically active noncovalent complex. This complex binds to the anti-Mullerian hormone receptor type 2 and causes the regression of Mullerian ducts in the male embryo that would otherwise differentiate into the uterus and fallopian tubes. This protein also plays a role in Leydig cell differentiation and function and follicular development in adult females. Mutations in this gene result in persistent Mullerian duct syndrome. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 19-2249605-C-T is Benign according to our data. Variant chr19-2249605-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 745907.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.018 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMH | NM_000479.5 | c.273C>T | p.Arg91= | synonymous_variant | 1/5 | ENST00000221496.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMH | ENST00000221496.5 | c.273C>T | p.Arg91= | synonymous_variant | 1/5 | 1 | NM_000479.5 | P1 | |
AMH | ENST00000592877.1 | n.297C>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152178Hom.: 1 Cov.: 34
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GnomAD3 exomes AF: 0.0000687 AC: 11AN: 160048Hom.: 0 AF XY: 0.0000453 AC XY: 4AN XY: 88342
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GnomAD4 exome AF: 0.0000738 AC: 103AN: 1395772Hom.: 0 Cov.: 34 AF XY: 0.0000551 AC XY: 38AN XY: 689272
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152296Hom.: 1 Cov.: 34 AF XY: 0.0000806 AC XY: 6AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
AMH-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at