9-12693928-G-C

Variant names:

• chr9-12693928-G-C
• rs181350173
• NM_000550.3:c.-69G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000550.3(TYRP1):​c.-69G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TYRP1 NM_000550.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.-69G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_000541.1	P17643
	TYRP1	NM_000550.3	MANE Select	c.-69G>C		5_prime_UTR	Exon 2 of 8	NP_000541.1	P17643

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.-69G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000373570.4	P17643
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.-69G>C		5_prime_UTR	Exon 2 of 8	ENSP00000373570.4	P17643
	TYRP1	ENST00000473763.1	TSL:4	c.-69G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	ENSP00000419006.1	C9JZ52

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.56
DANN	Benign	0.47
PhyloP100		-0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs181350173; hg19: chr9-12693928; COSMIC: COSV101141398; COSMIC: COSV101141398;