Variant 17-19705472-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001099646.3(SLC47A2):c.873G>T(p.Gln291His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,611,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SLC47A2
NM_001099646.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101

Variant links:

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]

SLC47A2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02108261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC47A2	NM_001099646.3 linkuse as main transcript	c.873G>T	p.Gln291His	missense_variant	10/17	ENST00000433844.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC47A2	ENST00000433844.4 linkuse as main transcript	c.873G>T	p.Gln291His	missense_variant	10/17	5	NM_001099646.3	P1	Q86VL8-3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000317

AC:

AN:

245936

Hom.:

AF XY:

0.000270

AC XY:

AN XY:

133478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000352

Gnomad ASJ exome

AF:

0.00552

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000808

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1459644

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

725996

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000427

Gnomad4 ASJ exome

AF:

0.00575

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000164

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000528

Hom.:

Bravo

AF:

0.000230

ExAC

AF:

0.000272

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.981G>T (p.Q327H) alteration is located in exon 10 (coding exon 10) of the SLC47A2 gene. This alteration results from a G to T substitution at nucleotide position 981, causing the glutamine (Q) at amino acid position 327 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.;.

Eigen

Benign

-0.081

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.013

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.20

B;D;.

Vest4

0.35

MutPred

0.68

Loss of stability (P = 0.0582);.;.;

MVP

0.081

MPC

0.51

ClinPred

0.20

GERP RS

4.0

Varity_R

0.62

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over