Genetic Variant SLC22A6:p.Val357Leu (chr11-62979917-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153276.3(SLC22A6):c.1069G>C(p.Val357Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SLC22A6
NM_153276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.185

Variant links:

Genes affected

SLC22A6 (HGNC:10970): (solute carrier family 22 member 6) The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SLC22A6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36443672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A6	NM_153276.3 link	c.1069G>C	p.Val357Leu	missense_variant	Exon 7 of 10	ENST00000360421.9	NP_695008.1	Q4U2R8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A6	ENST00000360421.9 link	c.1069G>C	p.Val357Leu	missense_variant	Exon 7 of 10	1	NM_153276.3	ENSP00000353597.4		Q4U2R8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251272

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1069G>C (p.V357L) alteration is located in exon 7 (coding exon 7) of the SLC22A6 gene. This alteration results from a G to C substitution at nucleotide position 1069, causing the valine (V) at amino acid position 357 to be replaced by a leucine (L). 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

Uncertain

0.53

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;.;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.36

T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.4

L;L;L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Benign

0.061

T;T;T;T

Polyphen

0.93

P;P;P;D

Vest4

0.39

MutPred

0.55

Loss of catalytic residue at V357 (P = 0.1388);Loss of catalytic residue at V357 (P = 0.1388);Loss of catalytic residue at V357 (P = 0.1388);Loss of catalytic residue at V357 (P = 0.1388);

MVP

0.76

MPC

0.57

ClinPred

0.89

GERP RS

4.4

Varity_R

0.53

gMVP

0.52

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