rs35866166

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000550.3(TYRP1):c.729T>C(p.Ser243Ser) 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

Publications

9 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 -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 VariationId 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 rank	MANE	Protein	UniProt
TYRP1	NM_000550.3 link	c.729T>C	p.Ser243Ser	synonymous_variant	Exon 4 of 8	ENST00000388918.10	NP_000541.1	P17643
TYRP1	XM_047423841.1 link	c.708+2634T>C		intron_variant	Intron 3 of 4		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10 link	c.729T>C	p.Ser243Ser	synonymous_variant	Exon 4 of 8	1	NM_000550.3	ENSP00000373570.4		P17643

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

GnomAD2 exomes

AF:

0.0453

AC:

11386

AN:

251162

AF XY:

0.0453

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 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

African (AFR)

AF:

0.0100

AC:

335

AN:

33462

American (AMR)

AF:

0.0248

AC:

1108

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.0713

AC:

1861

AN:

26118

East Asian (EAS)

AF:

0.000176

AC:

AN:

39674

South Asian (SAS)

AF:

0.0155

AC:

1335

AN:

86246

European-Finnish (FIN)

AF:

0.0800

AC:

4272

AN:

53406

Middle Eastern (MID)

AF:

0.0447

AC:

258

AN:

5768

European-Non Finnish (NFE)

AF:

0.0620

AC:

68876

AN:

1111504

Other (OTH)

AF:

0.0510

AC:

3079

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

4038

8077

12115

16154

20192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2500

5000

7500

10000

12500

<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:

0.0431

AC:

6558

AN:

152224

Hom.:

188

Cov.:

AF XY:

0.0433

AC XY:

3221

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0119

AC:

496

AN:

41558

American (AMR)

AF:

0.0301

AC:

459

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0757

AC:

263

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.0112

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0837

AC:

888

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0621

AC:

4225

AN:

68002

Other (OTH)

AF:

0.0449

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

306

612

918

1224

1530

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:

0.0552

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

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 12, 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

-0.61

CADD

Benign

5.3

(source)

DANN

Benign

0.75

PhyloP100

0.056

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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