19-2250700-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000479.5(AMH):c.604C>T(p.Arg202Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,539,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000479.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AMH | NM_000479.5 | c.604C>T | p.Arg202Cys | missense_variant | Exon 3 of 5 | ENST00000221496.5 | NP_000470.3 | |
MIR4321 | NR_036207.1 | n.62C>T | non_coding_transcript_exon_variant | Exon 1 of 1 | ||||
MIR4321 | unassigned_transcript_3189 | n.13C>T | non_coding_transcript_exon_variant | Exon 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMH | ENST00000221496.5 | c.604C>T | p.Arg202Cys | missense_variant | Exon 3 of 5 | 1 | NM_000479.5 | ENSP00000221496.2 | ||
AMH | ENST00000589313.2 | n.957C>T | non_coding_transcript_exon_variant | Exon 1 of 3 | 5 | |||||
MIR4321 | ENST00000592276.1 | n.62C>T | non_coding_transcript_exon_variant | Exon 1 of 1 | 6 | |||||
AMH | ENST00000592877.1 | n.485C>T | non_coding_transcript_exon_variant | Exon 2 of 2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000221 AC: 3AN: 135660Hom.: 0 AF XY: 0.0000404 AC XY: 3AN XY: 74256
GnomAD4 exome AF: 0.0000130 AC: 18AN: 1387062Hom.: 0 Cov.: 34 AF XY: 0.0000190 AC XY: 13AN XY: 684762
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine with cysteine at codon 202 of the AMH protein (p.Arg202Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with AMH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1355108). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at