rs377580634
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_002386.4(MC1R):c.583T>G(p.Phe195Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,606,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. F195F) has been classified as Likely benign.
Frequency
Consequence
NM_002386.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.583T>G | p.Phe195Val | missense_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.583T>G | p.Phe195Val | missense_variant | 1/1 | NM_002386.4 | P1 | ||
ENST00000554623.1 | n.971A>C | non_coding_transcript_exon_variant | 2/2 | 3 | |||||
MC1R | ENST00000555427.1 | c.583T>G | p.Phe195Val | missense_variant | 3/4 | 5 | |||
MC1R | ENST00000639847.1 | c.583T>G | p.Phe195Val | missense_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000411 AC: 1AN: 243414Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132662
GnomAD4 exome AF: 0.0000468 AC: 68AN: 1454368Hom.: 0 Cov.: 35 AF XY: 0.0000553 AC XY: 40AN XY: 723720
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
Melanoma, cutaneous malignant, susceptibility to, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | ClinVar contains an entry for this variant (Variation ID: 239157). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with primary melanoma (PMID: 16982779). This variant is present in population databases (rs377580634, gnomAD 0.002%). This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 195 of the MC1R protein (p.Phe195Val). - |
Tyrosinase-positive oculocutaneous albinism;C1849452:Skin/hair/eye pigmentation, variation in, 2;C2751295:Melanoma, cutaneous malignant, susceptibility to, 5;C2751296:Increased analgesia from kappa-opioid receptor agonist, female-specific Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at