rs121912778
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000388918.10(TYRP1):c.1120C>T(p.Arg374Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,786 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. R374R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000388918.10 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TYRP1 | NM_000550.3 | c.1120C>T | p.Arg374Ter | stop_gained | 6/8 | ENST00000388918.10 | NP_000541.1 | |
LURAP1L-AS1 | NR_125775.1 | n.317-3938G>A | intron_variant, non_coding_transcript_variant | |||||
TYRP1 | XM_047423841.1 | c.915C>T | p.Phe305= | synonymous_variant | 5/5 | XP_047279797.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TYRP1 | ENST00000388918.10 | c.1120C>T | p.Arg374Ter | stop_gained | 6/8 | 1 | NM_000550.3 | ENSP00000373570 | P1 | |
LURAP1L-AS1 | ENST00000417638.1 | n.273-3938G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 151986Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250744Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135550
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1460800Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 726708
GnomAD4 genome AF: 0.0000592 AC: 9AN: 151986Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74252
ClinVar
Submissions by phenotype
Oculocutaneous albinism type 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2005 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 22, 2023 | This sequence change creates a premature translational stop signal (p.Arg374*) in the TYRP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYRP1 are known to be pathogenic (PMID: 8651291, 9345097). This variant is present in population databases (rs121912778, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism type 3 (PMID: 15996218). It has also been observed to segregate with disease in related individuals. This variant is also known as p.R373X (c.1117C>T). ClinVar contains an entry for this variant (Variation ID: 17595). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at