chr9-12694063-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM1BP4_StrongBP6_Very_Strong

The NM_000550.3(TYRP1):c.67C>T(p.Arg23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000762 in 1,613,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 1 hom. )

Consequence

TYRP1
NM_000550.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.108

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 6 uncertain in NM_000550.3

BP4

Computational evidence support a benign effect (MetaRNN=0.0048153102).

BP6

Variant 9-12694063-C-T is Benign according to our data. Variant chr9-12694063-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 913604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3 link	c.67C>T	p.Arg23Trp	missense_variant	Exon 2 of 8	ENST00000388918.10	NP_000541.1	P17643
TYRP1	XM_047423841.1 link	c.67C>T	p.Arg23Trp	missense_variant	Exon 2 of 5		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TYRP1	ENST00000388918.10 link	c.67C>T	p.Arg23Trp	missense_variant	Exon 2 of 8	1	NM_000550.3	ENSP00000373570.4	P17643
TYRP1	ENST00000473763.1 link	c.67C>T	p.Arg23Trp	missense_variant	Exon 2 of 2	4		ENSP00000419006.1	C9JZ52
TYRP1	ENST00000459790.1 link	n.322C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000803

AC:

122

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000919

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000621

AC:

156

AN:

251050

AF XY:

0.000649

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.000767

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000758

AC:

1108

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

547

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.000537

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26134

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39694

Gnomad4 SAS exome

AF:

0.000325

AC:

AN:

86256

Gnomad4 FIN exome

AF:

0.00114

AC:

AN:

53414

Gnomad4 NFE exome

AF:

0.000847

AC:

942

AN:

1112008

Gnomad4 Remaining exome

AF:

0.000695

AC:

AN:

60396

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.000802

AC:

122

AN:

152078

Hom.:

Cov.:

AF XY:

0.000955

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000434

AC:

0.000433756

AN:

0.000433756

Gnomad4 AMR

AF:

0.000918

AC:

0.000917551

AN:

0.000917551

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000415

AC:

0.000415282

AN:

0.000415282

Gnomad4 FIN

AF:

0.00330

AC:

0.00330438

AN:

0.00330438

Gnomad4 NFE

AF:

0.000735

AC:

0.000735359

AN:

0.000735359

Gnomad4 OTH

AF:

0.00142

AC:

0.00142045

AN:

0.00142045

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.000831

Hom.:

Bravo

AF:

0.000631

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oculocutaneous albinism type 3

Benign:1

Apr 28, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.16

CADD

Benign

3.9

DANN

Benign

0.48

DEOGEN2

Benign

0.063

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.095

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.0048

T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

-1.0

.;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.86

N;N

REVEL

Uncertain

0.32

Sift

Benign

0.56

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0020

.;B

Vest4

0.11

MVP

0.84

MPC

0.0057

ClinPred

0.0017

GERP RS

-1.7

Varity_R

0.037

gMVP

0.56

Mutation Taster

=94/6

polymorphism

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