5-33946466-A-G

Position:

• chr5-33946466-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012509.4(SLC45A2):​c.*682T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 985,534 control chromosomes in the GnomAD database, including 425,705 homozygotes. 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: 𝑓 0.72 (45957 hom., cov: 33)
  • Exomes 𝑓: 0.94 (379748 hom.)
• Consequence: SLC45A2 NM_001012509.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1368+697T>C		intron_variant		ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.*682T>C		3_prime_UTR_variant	6/6		NP_001012527.2
SLC45A2	XM_047417259.1	c.1128+697T>C		intron_variant			XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000382102	c.*682T>C		3_prime_UTR_variant	6/6	1		ENSP00000371534.3
SLC45A2	ENST00000296589.9	c.1368+697T>C		intron_variant		1	NM_016180.5	ENSP00000296589.4

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109163 AN: 152120 Hom.: 45943 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.695

GnomAD4 exome AF: 0.942 AC: 785300 AN: 833296 Hom.: 379748 Cov.: 41 AF XY: 0.942 AC XY: 362503 AN XY: 384804

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.935

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.996

Gnomad4 NFE exome AF: 0.980

Gnomad4 OTH exome AF: 0.824

GnomAD4 genome AF: 0.717 AC: 109206 AN: 152238 Hom.: 45957 Cov.: 33 AF XY: 0.704 AC XY: 52403 AN XY: 74446

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.694

Alfa AF: 0.857 Hom.: 32429

Bravo AF: 0.676

Asia WGS AF: 0.263 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.53

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: rs35407; hg19: chr5-33946571;