rs61754361
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000372.5(TYR):c.572del(p.Gly191AspfsTer35) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. G190G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000372.5 frameshift
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.572del | p.Gly191AspfsTer35 | frameshift_variant | 1/5 | ENST00000263321.6 | |
TYR | XM_011542970.3 | c.572del | p.Gly191AspfsTer35 | frameshift_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYR | ENST00000263321.6 | c.572del | p.Gly191AspfsTer35 | frameshift_variant | 1/5 | 1 | NM_000372.5 | P1 | |
TYR | ENST00000526139.1 | n.633del | non_coding_transcript_exon_variant | 1/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251458Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135894
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727246
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
Tyrosinase-negative oculocutaneous albinism Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1991 | - - |
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 | Oct 23, 2015 | - - |
not provided Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change creates a premature translational stop signal (p.Gly191Aspfs*35) 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 (rs61754361, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism (PMID: 1905879). ClinVar contains an entry for this variant (Variation ID: 99570). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2021 | Frameshift 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: 1905879) - |
not provided, no classification provided | literature only | Retina International | - | - - |
SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 25, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at