chr9-12708269-C-T

Variant names:

• chr9-12708269-C-T
• rs17280629
• NM_000550.3:c.1408+126C>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.1408+126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 1,192,332 control chromosomes in the GnomAD database, including 2,114 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 0.056 (264 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1850 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0608 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.1408+126C>T		intron	N/A	NP_000541.1
	LURAP1L-AS1	NR_125775.1		n.317-7643G>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.1408+126C>T		intron	N/A	ENSP00000373570.4
	TYRP1	ENST00000381136.2	TSL:2	c.538+126C>T		intron	N/A	ENSP00000370528.2
	TYRP1	ENST00000381142.3	TSL:2	n.499-708C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8505 AN: 151860 Hom.: 258 Cov.: 32

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0551

GnomAD4 exome AF: 0.0557 AC: 57948 AN: 1040354 Hom.: 1850 AF XY: 0.0542 AC XY: 28595 AN XY: 527702

African (AFR) AF: 0.0539 AC: 1295 AN: 24044

American (AMR) AF: 0.0278 AC: 947 AN: 34022

Ashkenazi Jewish (ASJ) AF: 0.0707 AC: 1529 AN: 21638

East Asian (EAS) AF: 0.000117 AC: 4 AN: 34104

South Asian (SAS) AF: 0.0157 AC: 1086 AN: 68986

European-Finnish (FIN) AF: 0.0799 AC: 3895 AN: 48766

Middle Eastern (MID) AF: 0.0487 AC: 218 AN: 4472

European-Non Finnish (NFE) AF: 0.0613 AC: 46523 AN: 758564

Other (OTH) AF: 0.0536 AC: 2451 AN: 45758

GnomAD4 genome AF: 0.0562 AC: 8543 AN: 151978 Hom.: 264 Cov.: 32 AF XY: 0.0560 AC XY: 4158 AN XY: 74264

African (AFR) AF: 0.0570 AC: 2366 AN: 41486

American (AMR) AF: 0.0354 AC: 539 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 263 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5142

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4828

European-Finnish (FIN) AF: 0.0842 AC: 893 AN: 10600

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0623 AC: 4234 AN: 67916

Other (OTH) AF: 0.0540 AC: 114 AN: 2110

Alfa AF: 0.0583 Hom.: 28

Bravo AF: 0.0528

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.089
DANN	Benign	0.42
PhyloP100		-0.81
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: rs17280629; hg19: chr9-12708269;