chr16-89919506-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002386.4(MC1R):c.248C>T(p.Ser83Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,022 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S83P) has been classified as Likely benign.
Frequency
Consequence
NM_002386.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.248C>T | p.Ser83Leu | missense_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.248C>T | p.Ser83Leu | missense_variant | 1/1 | NM_002386.4 | P1 | ||
MC1R | ENST00000555427.1 | c.248C>T | p.Ser83Leu | missense_variant | 3/4 | 5 | |||
MC1R | ENST00000639847.1 | c.248C>T | p.Ser83Leu | missense_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000724 AC: 18AN: 248702Hom.: 0 AF XY: 0.0000667 AC XY: 9AN XY: 135024
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1460790Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 726640
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Melanoma, cutaneous malignant, susceptibility to, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 83 of the MC1R protein (p.Ser83Leu). This variant is present in population databases (rs777024553, gnomAD 0.01%). This missense change has been observed in individual(s) with melanoma as well as in unaffected control individuals (PMID: 15221796, 19585506, 20876876, 23522749, 23647022). ClinVar contains an entry for this variant (Variation ID: 470703). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MC1R protein function. Experimental studies have shown that this missense change affects MC1R function (PMID: 23522749). 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