chr9-12698471-T-C

Variant names:

• chr9-12698471-T-C
• rs35866166
• NM_000550.3:c.729T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000550.3(TYRP1):​c.729T>C​(p.Ser243Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,613,454 control chromosomes in the GnomAD database, including 2,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (188 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2521 hom.)
• Consequence: TYRP1 NM_000550.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0560

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 9-12698471-T-C is Benign according to our data. Variant chr9-12698471-T-C is described in ClinVar as [Benign]. Clinvar id is 256647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.056 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.729T>C	p.Ser243Ser	synonymous_variant	Exon 4 of 8	ENST00000388918.10	NP_000541.1
TYRP1	XM_047423841.1	c.708+2634T>C		intron_variant	Intron 3 of 4		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.729T>C	p.Ser243Ser	synonymous_variant	Exon 4 of 8	1	NM_000550.3	ENSP00000373570.4
TYRP1	ENST00000381136.2	c.43+2634T>C		intron_variant	Intron 1 of 4	2		ENSP00000370528.2
TYRP1	ENST00000381142.3	n.-35T>C		upstream_gene_variant		2
LURAP1L-AS1	ENST00000650458.1	n.*83A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6559 AN: 152106 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0458

GnomAD3 exomes AF: 0.0453 AC: 11386 AN: 251162 Hom.: 340 AF XY: 0.0453 AC XY: 6153 AN XY: 135740

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.0238

Gnomad ASJ exome AF: 0.0683

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0157

Gnomad FIN exome AF: 0.0815

Gnomad NFE exome AF: 0.0629

Gnomad OTH exome AF: 0.0506

GnomAD4 exome AF: 0.0555 AC: 81131 AN: 1461230 Hom.: 2521 Cov.: 32 AF XY: 0.0544 AC XY: 39511 AN XY: 726924

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.0248

Gnomad4 ASJ exome AF: 0.0713

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0155

Gnomad4 FIN exome AF: 0.0800

Gnomad4 NFE exome AF: 0.0620

Gnomad4 OTH exome AF: 0.0510

GnomAD4 genome AF: 0.0431 AC: 6558 AN: 152224 Hom.: 188 Cov.: 32 AF XY: 0.0433 AC XY: 3221 AN XY: 74430

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0757

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0552 Hom.: 118

Bravo AF: 0.0387

Asia WGS AF: 0.00751 AC: 27 AN: 3478

EpiCase AF: 0.0591

EpiControl AF: 0.0617

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oculocutaneous albinism type 3 Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.3
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs35866166; hg19: chr9-12698471; COSMIC: COSV66357973; COSMIC: COSV66357973;