chr9-12694255-C-A

Position:

chr9-12694255-C-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000550.3(TYRP1):c.259C>A(p.Arg87Arg) 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 1,613,566 control chromosomes in the GnomAD database, including 2,702 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: 0.055 ( 2514 hom. )

Consequence

TYRP1
NM_000550.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.35

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 9-12694255-C-A is Benign according to our data. Variant chr9-12694255-C-A is described in ClinVar as [Benign]. Clinvar id is 256644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0605 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.259C>A	p.Arg87Arg	synonymous_variant	2/8	ENST00000388918.10	NP_000541.1	P17643
TYRP1	XM_047423841.1 linkuse as main transcript	c.259C>A	p.Arg87Arg	synonymous_variant	2/5		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TYRP1	ENST00000388918.10 linkuse as main transcript	c.259C>A	p.Arg87Arg	synonymous_variant	2/8	1	NM_000550.3	ENSP00000373570.4	P17643
TYRP1	ENST00000473763.1 linkuse as main transcript	c.259C>A	p.Arg87Arg	synonymous_variant	2/2	4		ENSP00000419006.1	C9JZ52
TYRP1	ENST00000459790.1 linkuse as main transcript	n.514C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6545

AN:

152068

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0620

Gnomad OTH

AF:

0.0454

GnomAD3 exomes

AF:

0.0450

AC:

11227

AN:

249496

Hom.:

325

AF XY:

0.0449

AC XY:

6053

AN XY:

134846

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.0682

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0146

Gnomad FIN exome

AF:

0.0813

Gnomad NFE exome

AF:

0.0626

Gnomad OTH exome

AF:

0.0513

GnomAD4 exome

AF:

0.0555

AC:

81055

AN:

1461382

Hom.:

2514

Cov.:

AF XY:

0.0542

AC XY:

39436

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.00995

Gnomad4 AMR exome

AF:

0.0246

Gnomad4 ASJ exome

AF:

0.0714

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0144

Gnomad4 FIN exome

AF:

0.0800

Gnomad4 NFE exome

AF:

0.0620

Gnomad4 OTH exome

AF:

0.0510

GnomAD4 genome

AF:

0.0430

AC:

6544

AN:

152184

Hom.:

188

Cov.:

AF XY:

0.0432

AC XY:

3213

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.0299

Gnomad4 ASJ

AF:

0.0755

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.0839

Gnomad4 NFE

AF:

0.0620

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0488

Hom.:

Bravo

AF:

0.0386

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0589

EpiControl

AF:

0.0614

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 13, 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

-0.22

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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