Variant 6-160132354-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003057.3(SLC22A1):c.638G>C(p.Ser213Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.82

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38815305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC22A1	NM_003057.3 linkuse as main transcript	c.638G>C	p.Ser213Thr	missense_variant	3/11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2 linkuse as main transcript	c.638G>C	p.Ser213Thr	missense_variant	3/10		NP_694857.1
SLC22A1	XM_005267103.3 linkuse as main transcript	c.638G>C	p.Ser213Thr	missense_variant	3/12		XP_005267160.1
SLC22A1	XM_006715552.3 linkuse as main transcript	c.638G>C	p.Ser213Thr	missense_variant	3/9		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 linkuse as main transcript	c.638G>C	p.Ser213Thr	missense_variant	3/11	1	NM_003057.3	ENSP00000355930	P1	O15245-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

246096

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

132908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456806

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Feb 28, 2024

The c.638G>C (p.S213T) alteration is located in exon 3 (coding exon 3) of the SLC22A1 gene. This alteration results from a G to C substitution at nucleotide position 638, causing the serine (S) at amino acid position 213 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;.;.;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

.;T;T;T;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.5

L;L;L;L;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

N;.;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.24

T;.;T;T;T

Sift4G

Benign

0.48

T;.;T;T;D

Polyphen

0.13

B;B;P;.;.

Vest4

0.63

MutPred

0.59

Loss of MoRF binding (P = 0.1298);Loss of MoRF binding (P = 0.1298);Loss of MoRF binding (P = 0.1298);Loss of MoRF binding (P = 0.1298);.;

MVP

0.42

MPC

0.56

ClinPred

0.69

GERP RS

4.3

Varity_R

0.54

gMVP

0.38

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