Variant 6-160122053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003057.3(SLC22A1):c.118G>A(p.Val40Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,613,914 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 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22931767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC22A1	NM_003057.3 linkuse as main transcript	c.118G>A	p.Val40Ile	missense_variant	1/11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2 linkuse as main transcript	c.118G>A	p.Val40Ile	missense_variant	1/10		NP_694857.1
SLC22A1	XM_005267103.3 linkuse as main transcript	c.118G>A	p.Val40Ile	missense_variant	1/12		XP_005267160.1
SLC22A1	XM_006715552.3 linkuse as main transcript	c.118G>A	p.Val40Ile	missense_variant	1/9		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 linkuse as main transcript	c.118G>A	p.Val40Ile	missense_variant	1/11	1	NM_003057.3	ENSP00000355930	P1	O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251354

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

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:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000780

AC:

114

AN:

1461686

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000268

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:

0.0000836

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000761

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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 23, 2023

The c.118G>A (p.V40I) 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 118, causing the valine (V) at amino acid position 40 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

T;T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

.;D;D;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.1

M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.80

N;.;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.030

D;.;D;D

Sift4G

Benign

0.075

T;.;T;T

Polyphen

0.75

P;P;P;.

Vest4

0.091

MVP

0.53

MPC

0.15

ClinPred

0.11

GERP RS

4.6

Varity_R

0.16

gMVP

0.40

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