Genetic Variant TYRP1:c.*908T>C (chr9-12710090-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000550.3(TYRP1):c.*908T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,626 control chromosomes in the GnomAD database, including 22,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 22586 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

TYRP1
NM_000550.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.476

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-12710090-T-C is Benign according to our data. Variant chr9-12710090-T-C is described in ClinVar as Benign. ClinVar VariationId is 364873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000550.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	NM_000550.3	MANE Select	c.*908T>C		3_prime_UTR	Exon 8 of 8	NP_000541.1	P17643
	LURAP1L-AS1	NR_125775.1		n.317-9464A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.*908T>C	3_prime_UTR	Exon 8 of 8	ENSP00000373570.4	P17643
LURAP1L-AS1	ENST00000417638.1	TSL:3	n.273-9464A>G	intron	N/A
LURAP1L-AS1	ENST00000650458.1		n.193-10735A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75313

AN:

151510

Hom.:

22577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.0203

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.508

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.497

AC:

75353

AN:

151626

Hom.:

22586

Cov.:

AF XY:

0.488

AC XY:

36173

AN XY:

74054

show subpopulations

African (AFR)

AF:

0.230

AC:

9550

AN:

41456

American (AMR)

AF:

0.443

AC:

6718

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1895

AN:

3468

East Asian (EAS)

AF:

0.0202

AC:

104

AN:

5156

South Asian (SAS)

AF:

0.236

AC:

1137

AN:

4822

European-Finnish (FIN)

AF:

0.719

AC:

7593

AN:

10558

Middle Eastern (MID)

AF:

0.469

AC:

134

AN:

286

European-Non Finnish (NFE)

AF:

0.689

AC:

46628

AN:

67708

Other (OTH)

AF:

0.504

AC:

1061

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1543

3086

4628

6171

7714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.624

Hom.:

35174

Bravo

AF:

0.469

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Oculocutaneous albinism type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

(source)

DANN

Benign

0.66

PhyloP100

-0.48

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over