rs34130495

Positions:

• chr6-160139792-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003057.3(SLC22A1):​c.1201G>A​(p.Gly401Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,605,600 control chromosomes in the GnomAD database, including 509 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 0.016 (24 hom., cov: 27)
  • Exomes 𝑓: 0.023 (485 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32

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=0.01881957).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2474/152048) while in subpopulation NFE AF= 0.0274 (1862/67982). AF 95% confidence interval is 0.0264. There are 24 homozygotes in gnomad4. There are 1175 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1201G>A	p.Gly401Ser	missense_variant	7/11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1201G>A	p.Gly401Ser	missense_variant	7/10		NP_694857.1
SLC22A1	XM_005267103.3	c.1201G>A	p.Gly401Ser	missense_variant	7/12		XP_005267160.1
SLC22A1	XM_006715552.3	c.1201G>A	p.Gly401Ser	missense_variant	7/9		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1201G>A	p.Gly401Ser	missense_variant	7/11	1	NM_003057.3	ENSP00000355930	P1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2473 AN: 151930 Hom.: 24 Cov.: 27

Gnomad AFR AF: 0.00438

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0161 AC: 3873 AN: 240596 Hom.: 52 AF XY: 0.0165 AC XY: 2152 AN XY: 130116

Gnomad AFR exome AF: 0.00508

Gnomad AMR exome AF: 0.00858

Gnomad ASJ exome AF: 0.00660

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00269

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.0262

Gnomad OTH exome AF: 0.0161

GnomAD4 exome AF: 0.0229 AC: 33236 AN: 1453552 Hom.: 485 Cov.: 36 AF XY: 0.0225 AC XY: 16277 AN XY: 722818

Gnomad4 AFR exome AF: 0.00389

Gnomad4 AMR exome AF: 0.00921

Gnomad4 ASJ exome AF: 0.00658

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00281

Gnomad4 FIN exome AF: 0.0176

Gnomad4 NFE exome AF: 0.0272

Gnomad4 OTH exome AF: 0.0188

GnomAD4 genome AF: 0.0163 AC: 2474 AN: 152048 Hom.: 24 Cov.: 27 AF XY: 0.0158 AC XY: 1175 AN XY: 74328

Gnomad4 AFR AF: 0.00437

Gnomad4 AMR AF: 0.00858

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.0274

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0232 Hom.: 82

Bravo AF: 0.0151

TwinsUK AF: 0.0267 AC: 99

ALSPAC AF: 0.0291 AC: 112

ESP6500AA AF: 0.00499 AC: 22

ESP6500EA AF: 0.0251 AC: 216

ExAC AF: 0.0161 AC: 1959

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	.;D;D;D
MetaRNN	Benign	0.019	T;T;T;T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Uncertain	2.9	M;M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.8	D;.;D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;.;D;D
Sift4G	Uncertain	0.023	D;.;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.53
MPC		0.60
ClinPred		0.033	T
GERP RS		5.1
Varity_R		0.84
gMVP		0.71

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: rs34130495; hg19: chr6-160560824;