5-33946038-A-G

Variant names:

• chr5-33946038-A-G
• rs35406
• ENST00000382102:c.*1110T>C

Variant summary

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

The NM_001012509.4(SLC45A2):​c.*1110T>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 0.0273 in 985,366 control chromosomes in the GnomAD database, including 2,107 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 0.066 (1221 hom., cov: 33)
  • Exomes 𝑓: 0.020 (886 hom.)
• Consequence: SLC45A2 NM_001012509.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1368+1125T>C		intron_variant	Intron 6 of 6	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.*1110T>C		3_prime_UTR_variant	Exon 6 of 6		NP_001012527.2
SLC45A2	XM_047417259.1	c.1128+1125T>C		intron_variant	Intron 6 of 6		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000382102	c.*1110T>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000371534.3
SLC45A2	ENST00000296589.9	c.1368+1125T>C		intron_variant	Intron 6 of 6	1	NM_016180.5	ENSP00000296589.4

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9992 AN: 152166 Hom.: 1212 Cov.: 33

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0969

GnomAD4 exome AF: 0.0202 AC: 16845 AN: 833082 Hom.: 886 Cov.: 28 AF XY: 0.0201 AC XY: 7715 AN XY: 384706

Gnomad4 AFR exome AF: 0.0281

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.0320

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.00362

Gnomad4 NFE exome AF: 0.0124

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0657 AC: 10012 AN: 152284 Hom.: 1221 Cov.: 33 AF XY: 0.0731 AC XY: 5447 AN XY: 74474

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0134

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0381 Hom.: 433

Bravo AF: 0.0851

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.57

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: rs35406; hg19: chr5-33946143;