9-12694004-C-A

Variant names:

• chr9-12694004-C-A
• NM_000550.3:c.8C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000550.3(TYRP1):​c.8C>A​(p.Ala3Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: TYRP1 NM_000550.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.100

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11909184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.8C>A	p.Ala3Asp	missense_variant	Exon 2 of 8	ENST00000388918.10	NP_000541.1
TYRP1	XM_047423841.1	c.8C>A	p.Ala3Asp	missense_variant	Exon 2 of 5		XP_047279797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.8C>A	p.Ala3Asp	missense_variant	Exon 2 of 8	1	NM_000550.3	ENSP00000373570.4
TYRP1	ENST00000473763.1	c.8C>A	p.Ala3Asp	missense_variant	Exon 2 of 2	4		ENSP00000419006.1
TYRP1	ENST00000459790.1	n.263C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oculocutaneous albinism type 3 Uncertain:1

Jul 30, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.42	T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.85	N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.064	T;T
Polyphen		0.090	.;B
Vest4		0.19
MutPred		0.18		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.99
MPC		0.0050
ClinPred		0.19	T
GERP RS		1.4
Varity_R		0.18
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-12694004;