rs147565972

chr9-12708958-T-TAchr9-12708958-T-TAATC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000550.3(TYRP1):c.1409-18dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,602,834 control chromosomes in the GnomAD database, including 310,593 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (21667 hom., cov: 0)
  • Exomes 𝑓: 0.61 (288926 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.918

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]

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-12708958-T-TA is Benign according to our data. Variant chr9-12708958-T-TA is described in ClinVar as [Benign]. Clinvar id is 256643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.1409-18dup		intron_variant		ENST00000388918.10
LURAP1L-AS1	NR_125775.1	n.317-8333_317-8332insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.1409-18dup		intron_variant		1	NM_000550.3	P1
LURAP1L-AS1	ENST00000417638.1	n.273-8333_273-8332insT		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73149 AN: 151718 Hom.: 21667 Cov.: 0

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.487

GnomAD3 exomes AF: 0.508 AC: 125401 AN: 246804 Hom.: 38129 AF XY: 0.508 AC XY: 67730 AN XY: 133414

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.564

Gnomad EAS exome AF: 0.00825

Gnomad SAS exome AF: 0.262

Gnomad FIN exome AF: 0.720

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.608 AC: 882367 AN: 1450998 Hom.: 288926 Cov.: 31 AF XY: 0.599 AC XY: 432924 AN XY: 722520

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.00443

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.715

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.482 AC: 73152 AN: 151836 Hom.: 21667 Cov.: 0 AF XY: 0.474 AC XY: 35215 AN XY: 74234

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.0111

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.481

Alfa AF: 0.505 Hom.: 2709

Asia WGS AF: 0.138 AC: 484 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Oculocutaneous albinism type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147565972; hg19: chr9-12708958;