rs387906561

Positions:

• chr9-12694100-CT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The ENST00000388918.10(TYRP1):​c.107del​(p.Leu36Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYRP1 ENST00000388918.10 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -1.10

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-12694100-CT-C is Pathogenic according to our data. Variant chr9-12694100-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 17597.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-12694100-CT-C is described in Lovd as [Pathogenic]. Variant chr9-12694100-CT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.107del	p.Leu36Ter	frameshift_variant	2/8	ENST00000388918.10	NP_000541.1
TYRP1	XM_047423841.1	c.107del	p.Leu36Ter	frameshift_variant	2/5		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.107del	p.Leu36Ter	frameshift_variant	2/8	1	NM_000550.3	ENSP00000373570	P1
TYRP1	ENST00000473763.1	c.107del	p.Leu36Ter	frameshift_variant	2/2	4		ENSP00000419006
TYRP1	ENST00000459790.1	n.362del		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Oculocutaneous albinism type 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs387906561; hg19: chr9-12694100;