Genetic Variant TYRP1:c.*853A>C (chr9-12710035-A-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.*853A>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 0.485 in 151,738 control chromosomes in the GnomAD database, including 22,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 22237 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: -3.48

Publications

17 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=-0.98).

BP6

Variant 9-12710035-A-C is Benign according to our data. Variant chr9-12710035-A-C is described in ClinVar as Benign. ClinVar VariationId is 364872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 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.*853A>C		3_prime_UTR	Exon 8 of 8	NP_000541.1	P17643
	LURAP1L-AS1	NR_125775.1		n.317-9409T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.*853A>C	3_prime_UTR	Exon 8 of 8	ENSP00000373570.4	P17643
LURAP1L-AS1	ENST00000417638.1	TSL:3	n.273-9409T>G	intron	N/A
LURAP1L-AS1	ENST00000650458.1		n.193-10680T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73553

AN:

151620

Hom.:

22231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.0205

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.501

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:

0.485

AC:

73589

AN:

151738

Hom.:

22237

Cov.:

AF XY:

0.477

AC XY:

35361

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.188

AC:

7790

AN:

41490

American (AMR)

AF:

0.438

AC:

6654

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

1896

AN:

3464

East Asian (EAS)

AF:

0.0204

AC:

105

AN:

5156

South Asian (SAS)

AF:

0.237

AC:

1141

AN:

4824

European-Finnish (FIN)

AF:

0.719

AC:

7607

AN:

10584

Middle Eastern (MID)

AF:

0.473

AC:

138

AN:

292

European-Non Finnish (NFE)

AF:

0.689

AC:

46680

AN:

67740

Other (OTH)

AF:

0.498

AC:

1045

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1498

2996

4494

5992

7490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.596

Hom.:

35396

Bravo

AF:

0.455

Asia WGS

AF:

0.149

AC:

519

AN:

3468

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

-0.98

CADD

Benign

0.23

(source)

DANN

Benign

0.77

PhyloP100

-3.5

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