rs41302073
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The ENST00000388918.10(TYRP1):āc.1557T>Gā(p.Tyr519Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,612,736 control chromosomes in the GnomAD database, including 74 homozygotes. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.010 ( 36 hom., cov: 32)
Exomes š: 0.0011 ( 38 hom. )
Consequence
TYRP1
ENST00000388918.10 stop_gained
ENST00000388918.10 stop_gained
Scores
1
4
2
Clinical Significance
Conservation
PhyloP100: 3.45
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 Benign. Variant got -16 ACMG points.
BP6
Variant 9-12709125-T-G is Benign according to our data. Variant chr9-12709125-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 198743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1588/151986) while in subpopulation AFR AF= 0.0371 (1540/41492). AF 95% confidence interval is 0.0356. There are 36 homozygotes in gnomad4. There are 731 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 36 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TYRP1 | NM_000550.3 | c.1557T>G | p.Tyr519Ter | stop_gained | 8/8 | ENST00000388918.10 | NP_000541.1 | |
LURAP1L-AS1 | NR_125775.1 | n.317-8499A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TYRP1 | ENST00000388918.10 | c.1557T>G | p.Tyr519Ter | stop_gained | 8/8 | 1 | NM_000550.3 | ENSP00000373570 | P1 | |
LURAP1L-AS1 | ENST00000417638.1 | n.273-8499A>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0105 AC: 1589AN: 151868Hom.: 36 Cov.: 32
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GnomAD3 exomes AF: 0.00267 AC: 670AN: 250710Hom.: 17 AF XY: 0.00184 AC XY: 249AN XY: 135492
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GnomAD4 exome AF: 0.00107 AC: 1569AN: 1460750Hom.: 38 Cov.: 33 AF XY: 0.000892 AC XY: 648AN XY: 726688
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GnomAD4 genome AF: 0.0104 AC: 1588AN: 151986Hom.: 36 Cov.: 32 AF XY: 0.00984 AC XY: 731AN XY: 74280
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 08, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Oculocutaneous albinism type 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Oculocutaneous albinism type 3;C2677086:MELANESIAN BLOND HAIR Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 01, 2021 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at