NM_000550.3:c.1261+514C>A

Variant names:

• chr9-12705219-C-A
• rs2075509
• NM_000550.3:c.1261+514C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000550.3(TYRP1):​c.1261+514C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 152,044 control chromosomes in the GnomAD database, including 998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.047 (998 hom., cov: 32)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.1261+514C>A		intron_variant	Intron 6 of 7	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-4593G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.1261+514C>A		intron_variant	Intron 6 of 7	1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7121 AN: 151930 Hom.: 994 Cov.: 32

Gnomad AFR AF: 0.00836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.0629

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0469 AC: 7132 AN: 152044 Hom.: 998 Cov.: 32 AF XY: 0.0533 AC XY: 3961 AN XY: 74304

African (AFR) AF: 0.00833 AC: 346 AN: 41520

American (AMR) AF: 0.164 AC: 2494 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3468

East Asian (EAS) AF: 0.525 AC: 2687 AN: 5118

South Asian (SAS) AF: 0.0625 AC: 301 AN: 4814

European-Finnish (FIN) AF: 0.0309 AC: 328 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0120 AC: 818 AN: 67950

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0343 Hom.: 249

Bravo AF: 0.0595

Asia WGS AF: 0.266 AC: 923 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.1
DANN	Benign	0.44
PhyloP100		0.11
Mutation Taster		=99/1	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: rs2075509; hg19: chr9-12705219;