rs749525002
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002386.4(MC1R):c.613G>A(p.Val205Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,606,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V205V) has been classified as Likely benign.
Frequency
Consequence
NM_002386.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.613G>A | p.Val205Met | missense_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.613G>A | p.Val205Met | missense_variant | 1/1 | NM_002386.4 | P1 | ||
ENST00000554623.1 | n.941C>T | non_coding_transcript_exon_variant | 2/2 | 3 | |||||
MC1R | ENST00000555427.1 | c.613G>A | p.Val205Met | missense_variant | 3/4 | 5 | |||
MC1R | ENST00000639847.1 | c.613G>A | p.Val205Met | missense_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000331 AC: 8AN: 241722Hom.: 0 AF XY: 0.0000455 AC XY: 6AN XY: 131906
GnomAD4 exome AF: 0.000124 AC: 180AN: 1453860Hom.: 0 Cov.: 35 AF XY: 0.000124 AC XY: 90AN XY: 723436
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
ClinVar
Submissions by phenotype
Melanoma, cutaneous malignant, susceptibility to, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 205 of the MC1R protein (p.Val205Met). This variant is present in population databases (rs749525002, gnomAD 0.005%). This missense change has been observed in individual(s) with melanoma and basal cell carcinoma of skin (PMID: 16809487, 18067130). ClinVar contains an entry for this variant (Variation ID: 470708). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MC1R protein function. 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