NM_003057.3:c.156T>C

Variant names:

• chr6-160122091-T-C
• rs1867351
• NM_003057.3:c.156T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003057.3(SLC22A1):​c.156T>C​(p.Ser52Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,613,736 control chromosomes in the GnomAD database, including 40,562 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 0.25 (4864 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35698 hom.)
• Consequence: SLC22A1 NM_003057.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 47 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	NM_003057.3	MANE Select	c.156T>C	p.Ser52Ser	synonymous	Exon 1 of 11	NP_003048.1
	SLC22A1	NM_153187.2		c.156T>C	p.Ser52Ser	synonymous	Exon 1 of 10	NP_694857.1
	SLC22A1	NM_001437335.1		c.156T>C	p.Ser52Ser	synonymous	Exon 1 of 9	NP_001424264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.156T>C	p.Ser52Ser	synonymous	Exon 1 of 11	ENSP00000355930.4
	SLC22A1	ENST00000324965.8	TSL:5	c.156T>C	p.Ser52Ser	synonymous	Exon 1 of 10	ENSP00000318103.4
	SLC22A1	ENST00000457470.6	TSL:5	c.156T>C	p.Ser52Ser	synonymous	Exon 1 of 9	ENSP00000409557.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37351 AN: 152040 Hom.: 4852 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.249 AC: 62439 AN: 251230 AF XY: 0.239

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.398

Gnomad FIN exome AF: 0.223

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.216 AC: 316151 AN: 1461578 Hom.: 35698 Cov.: 34 AF XY: 0.215 AC XY: 156349 AN XY: 727098

African (AFR) AF: 0.308 AC: 10300 AN: 33480

American (AMR) AF: 0.344 AC: 15364 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3535 AN: 26136

East Asian (EAS) AF: 0.395 AC: 15667 AN: 39700

South Asian (SAS) AF: 0.202 AC: 17442 AN: 86258

European-Finnish (FIN) AF: 0.218 AC: 11601 AN: 53134

Middle Eastern (MID) AF: 0.161 AC: 931 AN: 5768

European-Non Finnish (NFE) AF: 0.205 AC: 228116 AN: 1111992

Other (OTH) AF: 0.219 AC: 13195 AN: 60388

GnomAD4 genome AF: 0.246 AC: 37410 AN: 152158 Hom.: 4864 Cov.: 33 AF XY: 0.245 AC XY: 18242 AN XY: 74376

African (AFR) AF: 0.303 AC: 12563 AN: 41530

American (AMR) AF: 0.274 AC: 4200 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2010 AN: 5144

South Asian (SAS) AF: 0.190 AC: 916 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2268 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14305 AN: 67982

Other (OTH) AF: 0.242 AC: 512 AN: 2116

Alfa AF: 0.215 Hom.: 4194

Bravo AF: 0.258

Asia WGS AF: 0.311 AC: 1085 AN: 3478

EpiCase AF: 0.213

EpiControl AF: 0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.4
DANN	Benign	0.41
PhyloP100		0.15
PromoterAI		0.0062	Neutral
Mutation Taster		=100/0	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: rs1867351; hg19: chr6-160543123; COSMIC: COSV61451750;