chr9-12694018-T-C

Variant names:

• chr9-12694018-T-C
• rs766047773
• NM_000550.3:c.22T>C

Variant summary

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

The NM_000550.3(TYRP1):​c.22T>C​(p.Ser8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TYRP1 NM_000550.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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=0.112843215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.22T>C	p.Ser8Pro	missense_variant	Exon 2 of 8	ENST00000388918.10	NP_000541.1
TYRP1	XM_047423841.1	c.22T>C	p.Ser8Pro	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.22T>C	p.Ser8Pro	missense_variant	Exon 2 of 8	1	NM_000550.3	ENSP00000373570.4
TYRP1	ENST00000473763.1	c.22T>C	p.Ser8Pro	missense_variant	Exon 2 of 2	4		ENSP00000419006.1
TYRP1	ENST00000459790.1	n.277T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250990 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	6.4
DANN	Benign	0.95
DEOGEN2	Benign	0.073	T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.49	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.79	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.19	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0040	.;B
Vest4		0.18
MutPred		0.52		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.97
MPC		0.0054
ClinPred		0.029	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs766047773; hg19: chr9-12694018;