chr9-12708958-T-TA

Variant names:

• chr9-12708958-T-TA
• rs147565972
• NM_000550.3:c.1409-18dupA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000550.3(TYRP1):​c.1409-18dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,602,834 control chromosomes in the GnomAD database, including 310,593 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (21667 hom., cov: 0)
  • Exomes 𝑓: 0.61 (288926 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.918
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 9-12708958-T-TA is Benign according to our data. Variant chr9-12708958-T-TA is described in ClinVar as Benign. ClinVar VariationId is 256643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 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.1409-18dupA		intron	N/A	NP_000541.1	P17643
	LURAP1L-AS1	NR_125775.1		n.317-8333dupT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.1409-18dupA		intron	N/A	ENSP00000373570.4	P17643
	TYRP1	ENST00000381136.2	TSL:2	c.539-18dupA		intron	N/A	ENSP00000370528.2	E7EQI3
	TYRP1	ENST00000381142.3	TSL:2	n.499-18dupA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73149 AN: 151718 Hom.: 21667 Cov.: 0

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.487

GnomAD2 exomes AF: 0.508 AC: 125401 AN: 246804 AF XY: 0.508

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.564

Gnomad EAS exome AF: 0.00825

Gnomad FIN exome AF: 0.720

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.608 AC: 882367 AN: 1450998 Hom.: 288926 Cov.: 31 AF XY: 0.599 AC XY: 432924 AN XY: 722520

African (AFR) AF: 0.188 AC: 6234 AN: 33190

American (AMR) AF: 0.441 AC: 19573 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 14665 AN: 26006

East Asian (EAS) AF: 0.00443 AC: 175 AN: 39542

South Asian (SAS) AF: 0.267 AC: 22959 AN: 85928

European-Finnish (FIN) AF: 0.715 AC: 37851 AN: 52948

Middle Eastern (MID) AF: 0.438 AC: 2516 AN: 5744

European-Non Finnish (NFE) AF: 0.675 AC: 745175 AN: 1103338

Other (OTH) AF: 0.554 AC: 33219 AN: 59912

GnomAD4 genome AF: 0.482 AC: 73152 AN: 151836 Hom.: 21667 Cov.: 0 AF XY: 0.474 AC XY: 35215 AN XY: 74234

African (AFR) AF: 0.205 AC: 8506 AN: 41466

American (AMR) AF: 0.426 AC: 6472 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1905 AN: 3464

East Asian (EAS) AF: 0.0111 AC: 57 AN: 5158

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4818

European-Finnish (FIN) AF: 0.717 AC: 7577 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45886 AN: 67848

Other (OTH) AF: 0.481 AC: 1014 AN: 2106

Alfa AF: 0.505 Hom.: 2709

Asia WGS AF: 0.138 AC: 484 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147565972; hg19: chr9-12708958;