6-160136611-C-T

Position:

• chr6-160136611-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366963.9(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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.037 (173 hom., cov: 32)
  • Exomes 𝑓: 0.025 (1153 hom.)
• Consequence: SLC22A1 ENST00000366963.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1022C>T	p.Pro341Leu	missense_variant	6/11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1022C>T	p.Pro341Leu	missense_variant	6/10		NP_694857.1
SLC22A1	XM_005267103.3	c.1022C>T	p.Pro341Leu	missense_variant	6/12		XP_005267160.1
SLC22A1	XM_006715552.3	c.1022C>T	p.Pro341Leu	missense_variant	6/9		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1022C>T	p.Pro341Leu	missense_variant	6/11	1	NM_003057.3	ENSP00000355930	P1

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

GnomAD3 exomes AF: 0.0376 AC: 9464 AN: 251482 Hom.: 375 AF XY: 0.0377 AC XY: 5123 AN XY: 135910

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 SAS exome AF: 0.0753

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

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.0735

Gnomad4 FIN exome AF: 0.00921

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0263

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

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0838

Gnomad4 FIN AF: 0.00810

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0182 Hom.: 108

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
MutationTaster	Benign	1.0	D;D;D
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

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