9-12685943-T-A

Position:

• chr9-12685943-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000473763.1(TYRP1):​c.-86+348T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,084 control chromosomes in the GnomAD database, including 22,540 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (22540 hom., cov: 32)
• Consequence: TYRP1 ENST00000473763.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000473763.1	c.-86+348T>A		intron_variant		4		ENSP00000419006

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75387 AN: 151966 Hom.: 22525 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.496 AC: 75436 AN: 152084 Hom.: 22540 Cov.: 32 AF XY: 0.488 AC XY: 36295 AN XY: 74340

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.499

Alfa AF: 0.591 Hom.: 3606

Bravo AF: 0.468

Asia WGS AF: 0.152 AC: 529 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.25
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13293905; hg19: chr9-12685943;