chr11-89178238-C-CA
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000372.5(TYR):c.286dupA(p.Met96AsnfsTer73) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000372.5 frameshift
Scores
Clinical Significance
Conservation
Publications
- oculocutaneous albinism type 1Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- oculocutaneous albinism type 1AInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
- Waardenburg syndrome type 2Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- minimal pigment oculocutaneous albinism type 1Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- oculocutaneous albinism type 1BInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- temperature-sensitive oculocutaneous albinism type 1Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251218 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727234 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Oculocutaneous albinism type 1A Pathogenic:3
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not provided Pathogenic:2Other:1
This sequence change creates a premature translational stop signal (p.Met96Asnfs*73) 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: 1905879). This variant is also known as a single base insertion at codon 96 resulting in a premature termination signal at codon 168. ClinVar contains an entry for this variant (Variation ID: 3788). For these reasons, this variant has been classified as Pathogenic. -
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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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 1905879) -
Abnormality of the skin Pathogenic:1
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SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at