rs34104736

Variant names:

• chr6-160132282-C-T
• rs34104736
• NM_003057.3:c.566C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016300857).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.566C>T	p.Ser189Leu	missense_variant	Exon 3 of 11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.566C>T	p.Ser189Leu	missense_variant	Exon 3 of 10		NP_694857.1
SLC22A1	NM_001437335.1	c.566C>T	p.Ser189Leu	missense_variant	Exon 3 of 9		NP_001424264.1
SLC22A1	XM_005267103.3	c.566C>T	p.Ser189Leu	missense_variant	Exon 3 of 12		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.566C>T	p.Ser189Leu	missense_variant	Exon 3 of 11	1	NM_003057.3	ENSP00000355930.4

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

GnomAD2 exomes AF: 0.00126 AC: 309 AN: 245374 AF XY: 0.00134

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 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

African (AFR) AF: 0.000330 AC: 11 AN: 33354

American (AMR) AF: 0.000549 AC: 24 AN: 43678

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.00170 AC: 144 AN: 84798

European-Finnish (FIN) AF: 0.00217 AC: 116 AN: 53360

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5750

European-Non Finnish (NFE) AF: 0.00190 AC: 2104 AN: 1109114

Other (OTH) AF: 0.00146 AC: 88 AN: 60180

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

African (AFR) AF: 0.000385 AC: 16 AN: 41558

American (AMR) AF: 0.00111 AC: 17 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68026

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00146 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
LIST_S2	Benign	0.67	.;T;T;T
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
PhyloP100		0.71
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs34104736; hg19: chr6-160553314;