rs765329261
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000372.5(TYR):c.753C>A(p.Tyr251Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,958 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. Y251Y) has been classified as Likely benign. 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.753C>A | p.Tyr251Ter | stop_gained | 1/5 | ENST00000263321.6 | |
TYR | XM_011542970.3 | c.753C>A | p.Tyr251Ter | stop_gained | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYR | ENST00000263321.6 | c.753C>A | p.Tyr251Ter | stop_gained | 1/5 | 1 | NM_000372.5 | P1 | |
TYR | ENST00000526139.1 | n.814C>A | non_coding_transcript_exon_variant | 1/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461850Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727232
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74288
ClinVar
Submissions by phenotype
Tyrosinase-negative oculocutaneous albinism Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 15, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change creates a premature translational stop signal (p.Tyr251*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism (PMID: 29345414, 30472657; Invitae). ClinVar contains an entry for this variant (Variation ID: 437175). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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