6-160136611-C-T

Variant names:

• chr6-160136611-C-T
• rs2282143
• NM_003057.3:c.1022C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003057.3(SLC22A1):​c.1022C>T​(p.Pro341Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0262 in 1,614,104 control chromosomes in the GnomAD database, including 1,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (173 hom., cov: 32)
  • Exomes 𝑓: 0.025 (1153 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• Publications: 117 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045109093).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1022C>T	p.Pro341Leu	missense_variant	Exon 6 of 11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1022C>T	p.Pro341Leu	missense_variant	Exon 6 of 10		NP_694857.1
SLC22A1	NM_001437335.1	c.1022C>T	p.Pro341Leu	missense_variant	Exon 6 of 9		NP_001424264.1
SLC22A1	XM_005267103.3	c.1022C>T	p.Pro341Leu	missense_variant	Exon 6 of 12		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1022C>T	p.Pro341Leu	missense_variant	Exon 6 of 11	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5562 AN: 152164 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.00810

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.0376 AC: 9464 AN: 251482 AF XY: 0.0377

Gnomad AFR exome AF: 0.0671

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.00878

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0251 AC: 36665 AN: 1461822 Hom.: 1153 Cov.: 32 AF XY: 0.0263 AC XY: 19135 AN XY: 727216

African (AFR) AF: 0.0691 AC: 2314 AN: 33474

American (AMR) AF: 0.0434 AC: 1940 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.151 AC: 6012 AN: 39698

South Asian (SAS) AF: 0.0735 AC: 6340 AN: 86254

European-Finnish (FIN) AF: 0.00921 AC: 492 AN: 53418

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5768

European-Non Finnish (NFE) AF: 0.0161 AC: 17876 AN: 1111964

Other (OTH) AF: 0.0263 AC: 1591 AN: 60386

GnomAD4 genome AF: 0.0366 AC: 5570 AN: 152282 Hom.: 173 Cov.: 32 AF XY: 0.0389 AC XY: 2899 AN XY: 74460

African (AFR) AF: 0.0668 AC: 2778 AN: 41556

American (AMR) AF: 0.0364 AC: 557 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.124 AC: 643 AN: 5166

South Asian (SAS) AF: 0.0838 AC: 404 AN: 4822

European-Finnish (FIN) AF: 0.00810 AC: 86 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1028 AN: 68032

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0229 Hom.: 369

Bravo AF: 0.0384

TwinsUK AF: 0.0165 AC: 61

ALSPAC AF: 0.0205 AC: 79

ESP6500AA AF: 0.0692 AC: 305

ESP6500EA AF: 0.0138 AC: 119

ExAC AF: 0.0384 AC: 4668

Asia WGS AF: 0.0920 AC: 321 AN: 3478

EpiCase AF: 0.0149

EpiControl AF: 0.0161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	.;D;D;D
MetaRNN	Benign	0.0045	T;T;T;T
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	3.9	H;H;H;H
PhyloP100		4.3
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-9.2	D;.;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;.;D;D
Sift4G	Uncertain	0.0080	D;.;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.28
MPC		0.58
ClinPred		0.10	T
GERP RS		4.6
Varity_R		0.74
gMVP		0.45
Mutation Taster		=80/20	polymorphism (auto)

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: rs2282143; hg19: chr6-160557643; COSMIC: COSV61451895; COSMIC: COSV61451895;