rs34104736

chr6-160132282-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003057.3(SLC22A1):c.566C>T(p.Ser189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,607,860 control chromosomes in the GnomAD database, including 2 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 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (2 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016300857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.566C>T	p.Ser189Leu	missense_variant	3/11	ENST00000366963.9
SLC22A1	NM_153187.2	c.566C>T	p.Ser189Leu	missense_variant	3/10
SLC22A1	XM_005267103.3	c.566C>T	p.Ser189Leu	missense_variant	3/12
SLC22A1	XM_006715552.3	c.566C>T	p.Ser189Leu	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.566C>T	p.Ser189Leu	missense_variant	3/11	1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00126 AC: 309 AN: 245374 Hom.: 1 AF XY: 0.00134 AC XY: 177 AN XY: 132508

Gnomad AFR exome AF: 0.000311

Gnomad AMR exome AF: 0.000523

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00154

Gnomad FIN exome AF: 0.00282

Gnomad NFE exome AF: 0.00151

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00171 AC: 2495 AN: 1455560 Hom.: 2 Cov.: 31 AF XY: 0.00170 AC XY: 1228 AN XY: 723806

Gnomad4 AFR exome AF: 0.000330

Gnomad4 AMR exome AF: 0.000549

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00170

Gnomad4 FIN exome AF: 0.00217

Gnomad4 NFE exome AF: 0.00190

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74476

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00194

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.00153 Hom.: 2

Bravo AF: 0.00121

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00120 AC: 146

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	8.9
Dann	Benign	0.67
DEOGEN2	Benign	0.40	T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.080	N
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.016	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.87	L;L;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.0	D;.;D;D
REVEL	Benign	0.11
Sift	Benign	0.21	T;.;T;T
Sift4G	Benign	0.69	T;.;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.35
MVP		0.15
MPC		0.12
ClinPred		0.0031	T
GERP RS		1.4
Varity_R		0.10
gMVP		0.54

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

Other links and lift over

dbSNP: rs34104736; hg19: chr6-160553314;