Variant 9-12704725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.07

Variant links:

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 links:

TYRP1 (HGNC:):

TYRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 256642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-12704725-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TYRP1	NM_000550.3 linkuse as main transcript	c.1261+20C>T	intron_variant	ENST00000388918.10	NP_000541.1	P17643
LURAP1L-AS1	NR_125775.1 linkuse as main transcript	n.317-4099G>A	intron_variant
TYRP1	XM_047423841.1 linkuse as main transcript	c.*128C>T	downstream_gene_variant		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10 linkuse as main transcript	c.1261+20C>T		intron_variant		1	NM_000550.3	ENSP00000373570.4		P17643

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62433

AN:

151736

Hom.:

16519

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.447

AC:

111897

AN:

250122

Hom.:

30244

AF XY:

0.448

AC XY:

60655

AN XY:

135246

show subpopulations

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 SAS exome

AF:

0.243

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.:

AF XY:

0.530

AC XY:

384129

AN XY:

724996

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.473

Gnomad4 EAS exome

AF:

0.0211

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.597

Gnomad4 OTH exome

AF:

0.489

GnomAD4 genome

AF:

0.411

AC:

62437

AN:

151854

Hom.:

16520

Cov.:

AF XY:

0.405

AC XY:

30070

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.376

Gnomad4 ASJ

AF:

0.460

Gnomad4 EAS

AF:

0.0201

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.626

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.443

Hom.:

4190

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.8

DANN

Benign

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over