rs62645917
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000372.5(TYR):c.1204C>T(p.Arg402Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,611,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R402R) has been classified as Pathogenic. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000372.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYR | NM_000372.5 | c.1204C>T | p.Arg402Ter | stop_gained | 4/5 | ENST00000263321.6 | |
TYR | XM_011542970.3 | c.1204C>T | p.Arg402Ter | stop_gained | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYR | ENST00000263321.6 | c.1204C>T | p.Arg402Ter | stop_gained | 4/5 | 1 | NM_000372.5 | P1 | |
TYR | ENST00000528243.1 | n.202C>T | non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 151760Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250344Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135326
GnomAD4 exome AF: 0.0000569 AC: 83AN: 1459762Hom.: 0 Cov.: 30 AF XY: 0.0000620 AC XY: 45AN XY: 726248
GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 151760Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74128
ClinVar
Submissions by phenotype
not provided Pathogenic:4Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 21, 2017 | - - |
not provided, no classification provided | literature only | Retina International | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | TYR: PVS1, PM3:Strong, PM2, PP4:Moderate - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 18326704, 8128955, 18463683, 29036293, 29437493, 29427439, 28976636, 34426522, 31589614, 28667292, 28266639, 35894802, 34838614, 33124154, 31077556) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | This sequence change creates a premature translational stop signal (p.Arg402*) in the TYR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYR are known to be pathogenic (PMID: 23504663). This variant is present in population databases (rs62645917, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 29345414). ClinVar contains an entry for this variant (Variation ID: 99542). For these reasons, this variant has been classified as Pathogenic. - |
Tyrosinase-negative oculocutaneous albinism Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 27, 2015 | - - |
Nonsyndromic Oculocutaneous Albinism Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Mar 07, 2017 | - - |
SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 16, 2023 | - - |
Abnormality of the skin Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Kariminejad - Najmabadi Pathology & Genetics Center | Jul 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at