6-160139792-G-A

Variant names:

• chr6-160139792-G-A
• rs34130495
• NM_003057.3:c.1201G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 136 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]

ENSG00000301636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

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.1201G>A	p.Gly401Ser	missense	Exon 7 of 11	NP_003048.1
	SLC22A1	NM_153187.2		c.1201G>A	p.Gly401Ser	missense	Exon 7 of 10	NP_694857.1
	SLC22A1	NM_001437335.1		c.1201G>A	p.Gly401Ser	missense	Exon 7 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.1201G>A	p.Gly401Ser	missense	Exon 7 of 11	ENSP00000355930.4
	SLC22A1	ENST00000324965.8	TSL:5	c.1201G>A	p.Gly401Ser	missense	Exon 7 of 10	ENSP00000318103.4
	SLC22A1	ENST00000457470.6	TSL:5	c.1201G>A	p.Gly401Ser	missense	Exon 7 of 9	ENSP00000409557.2

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

GnomAD2 exomes AF: 0.0161 AC: 3873 AN: 240596 AF XY: 0.0165

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 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

African (AFR) AF: 0.00389 AC: 128 AN: 32880

American (AMR) AF: 0.00921 AC: 392 AN: 42576

Ashkenazi Jewish (ASJ) AF: 0.00658 AC: 169 AN: 25686

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00281 AC: 238 AN: 84780

European-Finnish (FIN) AF: 0.0176 AC: 940 AN: 53310

Middle Eastern (MID) AF: 0.00646 AC: 37 AN: 5728

European-Non Finnish (NFE) AF: 0.0272 AC: 30206 AN: 1109054

Other (OTH) AF: 0.0188 AC: 1126 AN: 60008

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

African (AFR) AF: 0.00437 AC: 181 AN: 41454

American (AMR) AF: 0.00858 AC: 131 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4820

European-Finnish (FIN) AF: 0.0171 AC: 181 AN: 10564

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

European-Non Finnish (NFE) AF: 0.0274 AC: 1862 AN: 67982

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0223 Hom.: 178

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 v4.9

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
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.019	T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		9.3
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.53
MPC		0.60
ClinPred		0.033	T
GERP RS		5.1
Varity_R		0.84
gMVP		0.71
Mutation Taster		=87/13	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: rs34130495; hg19: chr6-160560824;