Variant chr9-12698471-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000550.3(TYRP1):c.729T>C(p.Ser243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,613,454 control chromosomes in the GnomAD database, including 2,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 188 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2521 hom. )

Consequence

TYRP1
NM_000550.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0560

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 9-12698471-T-C is Benign according to our data. Variant chr9-12698471-T-C is described in ClinVar as [Benign]. Clinvar id is 256647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.056 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRP1	NM_000550.3 linkuse as main transcript	c.729T>C	p.Ser243=	synonymous_variant	4/8	ENST00000388918.10	NP_000541.1
TYRP1	XM_047423841.1 linkuse as main transcript	c.708+2634T>C		intron_variant			XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TYRP1	ENST00000388918.10 linkuse as main transcript	c.729T>C	p.Ser243=	synonymous_variant	4/8	1	NM_000550.3	ENSP00000373570	P1
TYRP1	ENST00000381136.2 linkuse as main transcript	c.43+2634T>C		intron_variant		2		ENSP00000370528
TYRP1	ENST00000381142.3 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0431

AC:

6559

AN:

152106

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.0757

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0837

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0621

Gnomad OTH

AF:

0.0458

GnomAD3 exomes

AF:

0.0453

AC:

11386

AN:

251162

Hom.:

340

AF XY:

0.0453

AC XY:

6153

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.0683

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0157

Gnomad FIN exome

AF:

0.0815

Gnomad NFE exome

AF:

0.0629

Gnomad OTH exome

AF:

0.0506

GnomAD4 exome

AF:

0.0555

AC:

81131

AN:

1461230

Hom.:

2521

Cov.:

AF XY:

0.0544

AC XY:

39511

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.0248

Gnomad4 ASJ exome

AF:

0.0713

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0155

Gnomad4 FIN exome

AF:

0.0800

Gnomad4 NFE exome

AF:

0.0620

Gnomad4 OTH exome

AF:

0.0510

GnomAD4 genome

AF:

0.0431

AC:

6558

AN:

152224

Hom.:

188

Cov.:

AF XY:

0.0433

AC XY:

3221

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0301

Gnomad4 ASJ

AF:

0.0757

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.0837

Gnomad4 NFE

AF:

0.0621

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0552

Hom.:

118

Bravo

AF:

0.0387

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0591

EpiControl

AF:

0.0617

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.3

DANN

Benign

0.75

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