chr9-12693999-G-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000550.3(TYRP1):c.3G>T(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TYRP1
NM_000550.3 start_lost
NM_000550.3 start_lost
Scores
7
3
6
Clinical Significance
Conservation
PhyloP100: 2.95
Genes affected
TYRP1 (HGNC:12450): (tyrosinase related protein 1) This gene encodes a melanosomal enzyme that belongs to the tyrosinase family and plays an important role in the melanin biosynthetic pathway. Defects in this gene are the cause of rufous oculocutaneous albinism and oculocutaneous albinism type III. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-12693999-G-T is Pathogenic according to our data. Variant chr9-12693999-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 2714033.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYRP1 | NM_000550.3 | c.3G>T | p.Met1? | start_lost | 2/8 | ENST00000388918.10 | |
TYRP1 | XM_047423841.1 | c.3G>T | p.Met1? | start_lost | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYRP1 | ENST00000388918.10 | c.3G>T | p.Met1? | start_lost | 2/8 | 1 | NM_000550.3 | P1 | |
TYRP1 | ENST00000473763.1 | c.3G>T | p.Met1? | start_lost | 2/2 | 4 | |||
TYRP1 | ENST00000459790.1 | n.258G>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change affects the initiator methionine of the TYRP1 mRNA. The next in-frame methionine is located at codon 40. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TYRP1-related conditions. This variant disrupts a region of the TYRP1 protein in which other variant(s) (p.Pro27Arg) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
0.14
.;B
Vest4
0.68
MutPred
Gain of catalytic residue at L6 (P = 0.0244);Gain of catalytic residue at L6 (P = 0.0244);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.