11-89177976-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000372.5(TYR):c.25del(p.Leu9CysfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
TYR
NM_000372.5 frameshift
NM_000372.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.244
Genes affected
TYR (HGNC:12442): (tyrosinase) The enzyme encoded by this gene catalyzes the first 2 steps, and at least 1 subsequent step, in the conversion of tyrosine to melanin. The enzyme has both tyrosine hydroxylase and dopa oxidase catalytic activities, and requires copper for function. Mutations in this gene result in oculocutaneous albinism, and nonpathologic polymorphisms result in skin pigmentation variation. The human genome contains a pseudogene similar to the 3' half of this gene. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 586 pathogenic variants in the truncated region.
PM2
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Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYR | NM_000372.5 | c.25del | p.Leu9CysfsTer22 | frameshift_variant | 1/5 | ENST00000263321.6 | |
TYR | XM_011542970.3 | c.25del | p.Leu9CysfsTer22 | frameshift_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYR | ENST00000263321.6 | c.25del | p.Leu9CysfsTer22 | frameshift_variant | 1/5 | 1 | NM_000372.5 | P1 | |
TYR | ENST00000526139.1 | n.86del | non_coding_transcript_exon_variant | 1/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251454Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727228
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | literature only | Retina International | - | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at