chr6-160122326-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003057.3(SLC22A1):c.391G>A(p.Gly131Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000177 in 1,523,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

SLC22A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 1 of 11	ENST00000366963.9	NP_003048.1	O15245-1
SLC22A1	NM_153187.2 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 1 of 10		NP_694857.1	O15245-2
SLC22A1	XM_005267103.3 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 1 of 12		XP_005267160.1
SLC22A1	XM_006715552.3 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 1 of 9		XP_006715615.1	O15245-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 1 of 11	1	NM_003057.3	ENSP00000355930.4		O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181630

Hom.:

AF XY:

0.00

AC XY:

AN XY:

97818

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:

0.0000567

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1371334

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

673022

show subpopulations

Gnomad4 AFR exome

AF:

0.000361

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000406

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000468

Gnomad4 OTH exome

AF:

0.000106

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

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:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000826

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.391G>A (p.G131S) alteration is located in exon 1 (coding exon 1) of the SLC22A1 gene. This alteration results from a G to A substitution at nucleotide position 391, causing the glycine (G) at amino acid position 131 to be replaced by a serine (S). 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

Benign

0.12

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.75

D;D;D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.6

L;L;L;L

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.4

D;.;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.020

D;.;D;D

Sift4G

Benign

0.21

T;.;T;T

Polyphen

0.98

D;D;D;.

Vest4

0.54

MutPred

0.51

Loss of catalytic residue at G131 (P = 0.1037);Loss of catalytic residue at G131 (P = 0.1037);Loss of catalytic residue at G131 (P = 0.1037);Loss of catalytic residue at G131 (P = 0.1037);

MVP

0.50

MPC

0.58

ClinPred

0.98

GERP RS

5.4

Varity_R

0.50

gMVP

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over