rs4925042

Positions:

• chr17-19705460-G-A
• chr17-19705460-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001099646.3(SLC47A2):​c.885C>T​(p.Tyr295=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,610,510 control chromosomes in the GnomAD database, including 86,048 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 0.36 (10403 hom., cov: 31)
  • Exomes 𝑓: 0.31 (75645 hom.)
• Consequence: SLC47A2 NM_001099646.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

Genes affected

SLC47A2 (HGNC:26439): (solute carrier family 47 member 2) This gene encodes a protein belonging to a family of transporters involved in excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multidrug and toxin extrusion) protein family responsible for drug resistance. This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-2.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC47A2	NM_001099646.3	c.885C>T	p.Tyr295=	synonymous_variant	10/17	ENST00000433844.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC47A2	ENST00000433844.4	c.885C>T	p.Tyr295=	synonymous_variant	10/17	5	NM_001099646.3	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54672 AN: 151876 Hom.: 10395 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.369 AC: 90327 AN: 245016 Hom.: 18062 AF XY: 0.364 AC XY: 48337 AN XY: 132908

Gnomad AFR exome AF: 0.428

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.600

Gnomad SAS exome AF: 0.399

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.314 AC: 458443 AN: 1458516 Hom.: 75645 Cov.: 36 AF XY: 0.316 AC XY: 229393 AN XY: 725366

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.516

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.360 AC: 54706 AN: 151994 Hom.: 10403 Cov.: 31 AF XY: 0.365 AC XY: 27106 AN XY: 74300

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.369

Alfa AF: 0.320 Hom.: 12245

Bravo AF: 0.374

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.16
DANN	Benign	0.31

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: rs4925042; hg19: chr17-19608773; COSMIC: COSV57626441;