Variant chr9-12709305-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000550.3(TYRP1):c.*123C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,033,830 control chromosomes in the GnomAD database, including 181,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 20688 hom., cov: 33)

Exomes 𝑓: 0.57 ( 160476 hom. )

Consequence

TYRP1
NM_000550.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.369

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 9-12709305-C-A is Benign according to our data. Variant chr9-12709305-C-A is described in ClinVar as [Benign]. Clinvar id is 364861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRP1	NM_000550.3 linkuse as main transcript	c.*123C>A		3_prime_UTR_variant	8/8	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1 linkuse as main transcript	n.317-8679G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10 linkuse as main transcript	c.*123C>A		3_prime_UTR_variant	8/8	1	NM_000550.3	ENSP00000373570	P1
LURAP1L-AS1	ENST00000417638.1 linkuse as main transcript	n.273-8679G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71166

AN:

151676

Hom.:

20681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.709

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.575

AC:

507044

AN:

882036

Hom.:

160476

Cov.:

AF XY:

0.564

AC XY:

257913

AN XY:

457636

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.556

Gnomad4 EAS exome

AF:

0.00391

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.703

Gnomad4 NFE exome

AF:

0.660

Gnomad4 OTH exome

AF:

0.538

GnomAD4 genome

AF:

0.469

AC:

71198

AN:

151794

Hom.:

20688

Cov.:

AF XY:

0.463

AC XY:

34330

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.415

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.0113

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.709

Gnomad4 NFE

AF:

0.660

Gnomad4 OTH

AF:

0.469

Alfa

AF:

0.606

Hom.:

56505

Bravo

AF:

0.439

Asia WGS

AF:

0.138

AC:

482

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oculocutaneous albinism type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.67

DANN

Benign

0.29

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