chr9-12709068-G-A

Variant names:

• chr9-12709068-G-A
• rs34060600
• NM_000550.3:c.1500G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000550.3(TYRP1):​c.1500G>A​(p.Leu500Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,612,766 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L500L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0073 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (13 hom.)
• Consequence: TYRP1 NM_000550.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.272
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-12709068-G-A is Benign according to our data. Variant chr9-12709068-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 198744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.272 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00731 (1111/151948) while in subpopulation AFR AF = 0.025 (1036/41476). AF 95% confidence interval is 0.0237. There are 18 homozygotes in GnomAd4. There are 517 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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.1500G>A	p.Leu500Leu	synonymous	Exon 8 of 8	NP_000541.1	P17643
	LURAP1L-AS1	NR_125775.1		n.317-8442C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.1500G>A	p.Leu500Leu	synonymous	Exon 8 of 8	ENSP00000373570.4	P17643
	TYRP1	ENST00000381136.2	TSL:2	c.630G>A	p.Leu210Leu	synonymous	Exon 5 of 5	ENSP00000370528.2	E7EQI3
	TYRP1	ENST00000381142.3	TSL:2	n.590G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1110 AN: 151830 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00395

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00179 AC: 448 AN: 250634 AF XY: 0.00131

Gnomad AFR exome AF: 0.0248

Gnomad AMR exome AF: 0.000959

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000983

GnomAD4 exome AF: 0.000658 AC: 961 AN: 1460818 Hom.: 13 Cov.: 33 AF XY: 0.000541 AC XY: 393 AN XY: 726716

African (AFR) AF: 0.0240 AC: 803 AN: 33426

American (AMR) AF: 0.00126 AC: 56 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111368

Other (OTH) AF: 0.00131 AC: 79 AN: 60308

GnomAD4 genome AF: 0.00731 AC: 1111 AN: 151948 Hom.: 18 Cov.: 32 AF XY: 0.00696 AC XY: 517 AN XY: 74276

African (AFR) AF: 0.0250 AC: 1036 AN: 41476

American (AMR) AF: 0.00394 AC: 60 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67892

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00299 Hom.: 7

Bravo AF: 0.00870

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Oculocutaneous albinism type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

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: rs34060600; hg19: chr9-12709068;