9-12710090-T-C

Variant names:

• chr9-12710090-T-C
• rs1063380
• NM_000550.3:c.*908T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.476
• Publications: 9 publications found

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]

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

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.*908T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-9464A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.*908T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75313 AN: 151510 Hom.: 22577 Cov.: 32

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.497 AC: 75353 AN: 151626 Hom.: 22586 Cov.: 32 AF XY: 0.488 AC XY: 36173 AN XY: 74054

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

Alfa AF: 0.624 Hom.: 35174

Bravo AF: 0.469

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1063380; hg19: chr9-12710090;