9-12701897-A-T

Variant names:

• chr9-12701897-A-T
• rs2762463
• NM_000550.3:c.914-374A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000550.3(TYRP1):​c.914-374A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 192,970 control chromosomes in the GnomAD database, including 30,185 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 0.50 (22589 hom., cov: 31)
  • Exomes 𝑓: 0.56 (7596 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.95
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	NM_000550.3	MANE Select	c.914-374A>T		intron	N/A	NP_000541.1
	LURAP1L-AS1	NR_125775.1		n.317-1271T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.914-374A>T		intron	N/A	ENSP00000373570.4
	TYRP1	ENST00000381136.2	TSL:2	c.44-374A>T		intron	N/A	ENSP00000370528.2
	TYRP1	ENST00000381142.3	TSL:2	n.151-374A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76547 AN: 151626 Hom.: 22577 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.0205

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.565 AC: 23283 AN: 41224 Hom.: 7596 AF XY: 0.533 AC XY: 11489 AN XY: 21548

African (AFR) AF: 0.290 AC: 180 AN: 620

American (AMR) AF: 0.472 AC: 1510 AN: 3202

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 513 AN: 920

East Asian (EAS) AF: 0.0157 AC: 33 AN: 2096

South Asian (SAS) AF: 0.255 AC: 1402 AN: 5508

European-Finnish (FIN) AF: 0.724 AC: 1217 AN: 1682

Middle Eastern (MID) AF: 0.492 AC: 64 AN: 130

European-Non Finnish (NFE) AF: 0.685 AC: 17042 AN: 24864

Other (OTH) AF: 0.600 AC: 1322 AN: 2202

GnomAD4 genome AF: 0.505 AC: 76597 AN: 151746 Hom.: 22589 Cov.: 31 AF XY: 0.497 AC XY: 36825 AN XY: 74138

African (AFR) AF: 0.279 AC: 11557 AN: 41418

American (AMR) AF: 0.435 AC: 6620 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1936 AN: 3470

East Asian (EAS) AF: 0.0204 AC: 105 AN: 5156

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4826

European-Finnish (FIN) AF: 0.716 AC: 7506 AN: 10476

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.679 AC: 46059 AN: 67882

Other (OTH) AF: 0.503 AC: 1062 AN: 2112

Alfa AF: 0.491 Hom.: 1683

Bravo AF: 0.479

Asia WGS AF: 0.154 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0010
DANN	Benign	0.47
PhyloP100		-6.0
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: rs2762463; hg19: chr9-12701897;