9-12708269-C-T

Position:

• chr9-12708269-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.1408+126C>T		intron_variant		ENST00000388918.10
LURAP1L-AS1	NR_125775.1	n.317-7643G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.1408+126C>T		intron_variant		1	NM_000550.3	P1
LURAP1L-AS1	ENST00000417638.1	n.273-7643G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.0539

Gnomad4 AMR exome AF: 0.0278

Gnomad4 ASJ exome AF: 0.0707

Gnomad4 EAS exome AF: 0.000117

Gnomad4 SAS exome AF: 0.0157

Gnomad4 FIN exome AF: 0.0799

Gnomad4 NFE exome AF: 0.0613

Gnomad4 OTH exome AF: 0.0536

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

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0590 Hom.: 26

Bravo AF: 0.0528

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.089
DANN	Benign	0.42

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: rs17280629; hg19: chr9-12708269;