Variant chr6-160348765-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021977.4(SLC22A3):c.346G>T(p.Ala116Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000771 in 1,545,056 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0042 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

SLC22A3
NM_021977.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. [provided by RefSeq, Jul 2008]

SLC22A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003754288).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4 linkuse as main transcript	c.346G>T	p.Ala116Ser	missense_variant	1/11	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3 linkuse as main transcript	c.346G>T	p.Ala116Ser	missense_variant	1/11	1	NM_021977.4	ENSP00000275300	P1

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

632

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000855

AC:

122

AN:

142610

Hom.:

AF XY:

0.000625

AC XY:

AN XY:

78406

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.000567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000437

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000400

AC:

557

AN:

1392742

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

236

AN XY:

688238

show subpopulations

Gnomad4 AFR exome

AF:

0.0145

Gnomad4 AMR exome

AF:

0.000768

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000148

Gnomad4 OTH exome

AF:

0.000791

GnomAD4 genome

AF:

0.00417

AC:

635

AN:

152314

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

311

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.0000673

Hom.:

Bravo

AF:

0.00435

ESP6500AA

AF:

0.0121

AC:

ESP6500EA

AF:

0.000148

AC:

ExAC

AF:

0.000776

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.066

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.10

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.63

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

1.1

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.084

MVP

0.56

MPC

0.34

ClinPred

0.0031

GERP RS

3.6

Varity_R

0.095

gMVP

0.36

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over