9-12704725-C-T

Variant names:

• chr9-12704725-C-T
• rs2733832
• NM_000550.3:c.1261+20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000550.3(TYRP1):​c.1261+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,608,578 control chromosomes in the GnomAD database, including 243,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (16520 hom., cov: 32)
  • Exomes 𝑓: 0.54 (226544 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.07
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-12704725-C-T is Benign according to our data. Variant chr9-12704725-C-T is described in ClinVar as Benign. ClinVar VariationId is 256642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.1261+20C>T		intron_variant	Intron 6 of 7	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-4099G>A		intron_variant	Intron 3 of 3
TYRP1	XM_047423841.1	c.*128C>T		downstream_gene_variant			XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.1261+20C>T		intron_variant	Intron 6 of 7	1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62433 AN: 151736 Hom.: 16519 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.419

GnomAD2 exomes AF: 0.447 AC: 111897 AN: 250122 AF XY: 0.448

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.0141

Gnomad FIN exome AF: 0.629

Gnomad NFE exome AF: 0.596

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.537 AC: 782561 AN: 1456724 Hom.: 226544 Cov.: 33 AF XY: 0.530 AC XY: 384129 AN XY: 724996

African (AFR) AF: 0.111 AC: 3702 AN: 33340

American (AMR) AF: 0.395 AC: 17632 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12315 AN: 26056

East Asian (EAS) AF: 0.0211 AC: 838 AN: 39668

South Asian (SAS) AF: 0.248 AC: 21388 AN: 86160

European-Finnish (FIN) AF: 0.625 AC: 33031 AN: 52848

Middle Eastern (MID) AF: 0.366 AC: 2104 AN: 5748

European-Non Finnish (NFE) AF: 0.597 AC: 662089 AN: 1108120

Other (OTH) AF: 0.489 AC: 29462 AN: 60200

GnomAD4 genome AF: 0.411 AC: 62437 AN: 151854 Hom.: 16520 Cov.: 32 AF XY: 0.405 AC XY: 30070 AN XY: 74214

African (AFR) AF: 0.129 AC: 5342 AN: 41442

American (AMR) AF: 0.376 AC: 5731 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3466

East Asian (EAS) AF: 0.0201 AC: 103 AN: 5134

South Asian (SAS) AF: 0.219 AC: 1051 AN: 4810

European-Finnish (FIN) AF: 0.626 AC: 6612 AN: 10568

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40602 AN: 67890

Other (OTH) AF: 0.416 AC: 877 AN: 2108

Alfa AF: 0.444 Hom.: 4543

Bravo AF: 0.383

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oculocutaneous albinism type 3 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.48
PhyloP100		1.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2733832; hg19: chr9-12704725; COSMIC: COSV66358022; COSMIC: COSV66358022;