rs34509359

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. R87R) has been classified as Likely 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

Publications

12 publications found

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:

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

LURAP1L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TYRP1	NM_000550.3 link	c.259C>A	p.Arg87Arg	synonymous_variant	Exon 2 of 8	ENST00000388918.10	NP_000541.1	P17643
TYRP1	XM_047423841.1 link	c.259C>A	p.Arg87Arg	synonymous_variant	Exon 2 of 5		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10 link	c.259C>A	p.Arg87Arg	synonymous_variant	Exon 2 of 8	1	NM_000550.3	ENSP00000373570.4		P17643

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

GnomAD2 exomes

AF:

0.0450

AC:

11227

AN:

249496

AF XY:

0.0449

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 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

African (AFR)

AF:

0.00995

AC:

333

AN:

33480

American (AMR)

AF:

0.0246

AC:

1097

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0714

AC:

1864

AN:

26120

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39652

South Asian (SAS)

AF:

0.0144

AC:

1241

AN:

86174

European-Finnish (FIN)

AF:

0.0800

AC:

4272

AN:

53384

Middle Eastern (MID)

AF:

0.0444

AC:

256

AN:

5766

European-Non Finnish (NFE)

AF:

0.0620

AC:

68910

AN:

1111762

Other (OTH)

AF:

0.0510

AC:

3079

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

4935

9870

14806

19741

24676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2506

5012

7518

10024

12530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0430

AC:

6544

AN:

152184

Hom.:

188

Cov.:

AF XY:

0.0432

AC XY:

3213

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0120

AC:

498

AN:

41522

American (AMR)

AF:

0.0299

AC:

458

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

262

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.0104

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0839

AC:

888

AN:

10590

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0620

AC:

4218

AN:

68008

Other (OTH)

AF:

0.0445

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

318

636

955

1273

1591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0474

Hom.:

123

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.61

PhyloP100

1.3

Mutation Taster

=263/37

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over