rs34509359

Variant names:

• chr9-12694255-C-A
• rs34509359
• NM_000550.3:c.259C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-12694255-C-A
• chr9-12694255-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000550.3(TYRP1):​c.259C>A​(p.Arg87Arg) 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 1,613,566 control chromosomes in the GnomAD database, including 2,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R87R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.043 (188 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2514 hom.)
• Consequence: TYRP1 NM_000550.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35
• Publications: 12 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 9-12694255-C-A is Benign according to our data. Variant chr9-12694255-C-A is described in ClinVar as Benign. ClinVar VariationId is 256644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0605 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.259C>A	p.Arg87Arg	synonymous	Exon 2 of 8	NP_000541.1	P17643

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.259C>A	p.Arg87Arg	synonymous	Exon 2 of 8	ENSP00000373570.4	P17643
	TYRP1	ENST00000473763.1	TSL:4	c.259C>A	p.Arg87Arg	synonymous	Exon 2 of 2	ENSP00000419006.1	C9JZ52
	TYRP1	ENST00000459790.1	TSL:2	n.514C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6545 AN: 152068 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0454

GnomAD2 exomes AF: 0.0450 AC: 11227 AN: 249496 AF XY: 0.0449

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.0235

Gnomad ASJ exome AF: 0.0682

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0813

Gnomad NFE exome AF: 0.0626

Gnomad OTH exome AF: 0.0513

GnomAD4 exome AF: 0.0555 AC: 81055 AN: 1461382 Hom.: 2514 Cov.: 31 AF XY: 0.0542 AC XY: 39436 AN XY: 726934

African (AFR) AF: 0.00995 AC: 333 AN: 33480

American (AMR) AF: 0.0246 AC: 1097 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1864 AN: 26120

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39652

South Asian (SAS) AF: 0.0144 AC: 1241 AN: 86174

European-Finnish (FIN) AF: 0.0800 AC: 4272 AN: 53384

Middle Eastern (MID) AF: 0.0444 AC: 256 AN: 5766

European-Non Finnish (NFE) AF: 0.0620 AC: 68910 AN: 1111762

Other (OTH) AF: 0.0510 AC: 3079 AN: 60376

GnomAD4 genome AF: 0.0430 AC: 6544 AN: 152184 Hom.: 188 Cov.: 32 AF XY: 0.0432 AC XY: 3213 AN XY: 74390

African (AFR) AF: 0.0120 AC: 498 AN: 41522

American (AMR) AF: 0.0299 AC: 458 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4812

European-Finnish (FIN) AF: 0.0839 AC: 888 AN: 10590

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4218 AN: 68008

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.0474 Hom.: 123

Bravo AF: 0.0386

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.0589

EpiControl AF: 0.0614

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Oculocutaneous albinism type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		1.3
Mutation Taster		=263/37	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs34509359; hg19: chr9-12694255; COSMIC: COSV66357970; COSMIC: COSV66357970;