rs387907171

Variant names:

• chr9-12694273-C-A
• NM_000550.3:c.277C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-12694273-C-A
• chr9-12694273-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000550.3(TYRP1):​c.277C>A​(p.Arg93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R93H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TYRP1 NM_000550.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29868746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.277C>A	p.Arg93Ser	missense_variant	Exon 2 of 8	ENST00000388918.10	NP_000541.1
TYRP1	XM_047423841.1	c.277C>A	p.Arg93Ser	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.277C>A	p.Arg93Ser	missense_variant	Exon 2 of 8	1	NM_000550.3	ENSP00000373570.4
TYRP1	ENST00000473763.1	c.277C>A	p.Arg93Ser	missense_variant	Exon 2 of 2	4		ENSP00000419006.1
TYRP1	ENST00000459790.1	n.532C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727054

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: 0.0000207

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.91	D;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.28
Sift	Benign	0.039	D;T
Sift4G	Benign	0.077	T;D
Polyphen		0.81	.;P
Vest4		0.73
MutPred		0.38		Loss of MoRF binding (P = 0.1213);Loss of MoRF binding (P = 0.1213);
MVP		0.88
MPC		0.012
ClinPred		0.96	D
GERP RS		-0.32
Varity_R		0.74
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr9-12694273;