chr17-19705460-G-A

Variant names:

• chr17-19705460-G-A
• rs4925042
• NM_001099646.3:c.885C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001099646.3(SLC47A2):​c.885C>T​(p.Tyr295Tyr) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099646.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A2	NM_001099646.3	MANE Select	c.885C>T	p.Tyr295Tyr	synonymous	Exon 10 of 17	NP_001093116.1
	SLC47A2	NM_152908.5		c.993C>T	p.Tyr331Tyr	synonymous	Exon 10 of 17	NP_690872.2
	SLC47A2	NM_001256663.3		c.885C>T	p.Tyr295Tyr	synonymous	Exon 10 of 18	NP_001243592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A2	ENST00000433844.4	TSL:5 MANE Select	c.885C>T	p.Tyr295Tyr	synonymous	Exon 10 of 17	ENSP00000391848.3
	SLC47A2	ENST00000325411.9	TSL:1	c.993C>T	p.Tyr331Tyr	synonymous	Exon 10 of 17	ENSP00000326671.5
	SLC47A2	ENST00000350657.9	TSL:1	c.885C>T	p.Tyr295Tyr	synonymous	Exon 10 of 18	ENSP00000338084.6

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

GnomAD2 exomes AF: 0.369 AC: 90327 AN: 245016 AF XY: 0.364

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 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

African (AFR) AF: 0.430 AC: 14352 AN: 33380

American (AMR) AF: 0.492 AC: 21782 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 8197 AN: 26080

East Asian (EAS) AF: 0.516 AC: 20373 AN: 39500

South Asian (SAS) AF: 0.400 AC: 34340 AN: 85780

European-Finnish (FIN) AF: 0.272 AC: 14354 AN: 52790

Middle Eastern (MID) AF: 0.382 AC: 2190 AN: 5734

European-Non Finnish (NFE) AF: 0.290 AC: 322549 AN: 1110732

Other (OTH) AF: 0.337 AC: 20306 AN: 60276

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

African (AFR) AF: 0.426 AC: 17685 AN: 41468

American (AMR) AF: 0.446 AC: 6810 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3036 AN: 5146

South Asian (SAS) AF: 0.398 AC: 1910 AN: 4802

European-Finnish (FIN) AF: 0.265 AC: 2798 AN: 10566

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20247 AN: 67946

Other (OTH) AF: 0.369 AC: 780 AN: 2112

Alfa AF: 0.323 Hom.: 27473

Bravo AF: 0.374

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.16
DANN	Benign	0.31
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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