rs138272660
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000388918.10(TYRP1):c.1411C>T(p.Arg471Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000334 in 1,611,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. R471Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000388918.10 missense, splice_region
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TYRP1 | NM_000550.3 | c.1411C>T | p.Arg471Trp | missense_variant, splice_region_variant | 8/8 | ENST00000388918.10 | NP_000541.1 | |
LURAP1L-AS1 | NR_125775.1 | n.317-8353G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TYRP1 | ENST00000388918.10 | c.1411C>T | p.Arg471Trp | missense_variant, splice_region_variant | 8/8 | 1 | NM_000550.3 | ENSP00000373570 | P1 | |
LURAP1L-AS1 | ENST00000417638.1 | n.273-8353G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000375 AC: 57AN: 151854Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000368 AC: 92AN: 249704Hom.: 0 AF XY: 0.000437 AC XY: 59AN XY: 134996
GnomAD4 exome AF: 0.000330 AC: 482AN: 1459664Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 254AN XY: 726196
GnomAD4 genome AF: 0.000375 AC: 57AN: 151972Hom.: 0 Cov.: 32 AF XY: 0.000471 AC XY: 35AN XY: 74286
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 15, 2015 | - - |
Oculocutaneous albinism type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | May 01, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 471 of the TYRP1 protein (p.Arg471Trp). This variant is present in population databases (rs138272660, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TYRP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 212528). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Oculocutaneous albinism type 3;C2677086:MELANESIAN BLOND HAIR Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 26, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at