NM_000550.3:c.-69G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.-69G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 8	ENST00000388918.10	NP_000541.1
TYRP1	NM_000550.3	c.-69G>C		5_prime_UTR_variant	Exon 2 of 8	ENST00000388918.10	NP_000541.1
TYRP1	XM_047423841.1	c.-69G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5		XP_047279797.1
TYRP1	XM_047423841.1	c.-69G>C		5_prime_UTR_variant	Exon 2 of 5		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918	c.-69G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 8	1	NM_000550.3	ENSP00000373570.4
TYRP1	ENST00000388918	c.-69G>C		5_prime_UTR_variant	Exon 2 of 8	1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs181350173; hg19: chr9-12693928; COSMIC: COSV101141398; COSMIC: COSV101141398;