rs17346161

Positions:

• chr9-12705162-C-T

Variant summary

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

The NM_000550.3(TYRP1):​c.1261+457C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 152,010 control chromosomes in the GnomAD database, including 461 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 0.062 (461 hom., cov: 32)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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]

TYRP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.1261+457C>T		intron_variant		ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-4536G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.1261+457C>T		intron_variant		1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9398 AN: 151890 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0557

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

GnomAD4 genome AF: 0.0618 AC: 9398 AN: 152010 Hom.: 461 Cov.: 32 AF XY: 0.0616 AC XY: 4577 AN XY: 74286

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0943

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.0434

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.0749 Hom.: 291

Bravo AF: 0.0623

Asia WGS AF: 0.0230 AC: 82 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs17346161; hg19: chr9-12705162;