rs16891982

Variant names:

• chr5-33951588-C-A
• rs16891982
• NM_016180.5:c.1122G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-33951588-C-A
• chr5-33951588-C-G

Variant summary

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

The ENST00000510600.1(SLC45A2):​c.597G>T​(p.Leu199Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC45A2 ENST00000510600.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

Genes affected

SLC45A2 (HGNC:16472): (solute carrier family 45 member 2) This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1122G>T	p.Leu374Phe	missense_variant	Exon 5 of 7	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.1122G>T	p.Leu374Phe	missense_variant	Exon 5 of 6		NP_001012527.2
SLC45A2	XM_047417259.1	c.882G>T	p.Leu294Phe	missense_variant	Exon 5 of 7		XP_047273215.1
SLC45A2	NM_001297417.4	c.*64G>T		3_prime_UTR_variant	Exon 4 of 4		NP_001284346.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.1122G>T	p.Leu374Phe	missense_variant	Exon 5 of 7	1	NM_016180.5	ENSP00000296589.4
SLC45A2	ENST00000382102.7	c.1122G>T	p.Leu374Phe	missense_variant	Exon 5 of 6	1		ENSP00000371534.3
SLC45A2	ENST00000509381	c.*64G>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000421100.1
SLC45A2	ENST00000510600.1	c.597G>T	p.Leu199Phe	missense_variant	Exon 4 of 5	3		ENSP00000424010.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461858 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 727234

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74298

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D;.;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Pathogenic	3.0	M;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.20
MutPred		0.50		Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);.;
MVP		0.85
MPC		0.27
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.39
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16891982; hg19: chr5-33951693;