6-160348765-G-T

Variant names:

• chr6-160348765-G-T
• rs8187717
• NM_021977.4:c.346G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021977.4(SLC22A3):​c.346G>T​(p.Ala116Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000771 in 1,545,056 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: SLC22A3 NM_021977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 16 publications found

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003754288).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021977.4. 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
	SLC22A3	NM_021977.4	MANE Select	c.346G>T	p.Ala116Ser	missense	Exon 1 of 11	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.346G>T	p.Ala116Ser	missense	Exon 1 of 11	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.00415 AC: 632 AN: 152198 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000855 AC: 122 AN: 142610 AF XY: 0.000625

Gnomad AFR exome AF: 0.0146

Gnomad AMR exome AF: 0.000567

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.000240

GnomAD4 exome AF: 0.000400 AC: 557 AN: 1392742 Hom.: 4 Cov.: 65 AF XY: 0.000343 AC XY: 236 AN XY: 688238

African (AFR) AF: 0.0145 AC: 464 AN: 31942

American (AMR) AF: 0.000768 AC: 29 AN: 37774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 36390

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34574

Middle Eastern (MID) AF: 0.000187 AC: 1 AN: 5350

European-Non Finnish (NFE) AF: 0.0000148 AC: 16 AN: 1083722

Other (OTH) AF: 0.000791 AC: 46 AN: 58146

GnomAD4 genome AF: 0.00417 AC: 635 AN: 152314 Hom.: 4 Cov.: 33 AF XY: 0.00417 AC XY: 311 AN XY: 74494

African (AFR) AF: 0.0147 AC: 610 AN: 41592

American (AMR) AF: 0.00131 AC: 20 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.00435

ESP6500AA AF: 0.0121 AC: 40

ESP6500EA AF: 0.000148 AC: 1

ExAC AF: 0.000776 AC: 86

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.63	N
PhyloP100		1.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.084
MVP		0.56
MPC		0.34
ClinPred		0.0031	T
GERP RS		3.6
PromoterAI		0.024	Neutral
Varity_R		0.095
gMVP		0.36
Mutation Taster		=98/2	polymorphism

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: rs8187717; hg19: chr6-160769797;