chr6-160348765-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. 15/22 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.346G>T	p.Ala116Ser	missense_variant	Exon 1 of 11	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.346G>T	p.Ala116Ser	missense_variant	Exon 1 of 11	1	NM_021977.4	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

Gnomad4 AFR exome AF: 0.0145 AC: 464 AN: 31942

Gnomad4 AMR exome AF: 0.000768 AC: 29 AN: 37774

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25172

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 36390

Gnomad4 SAS exome AF: 0.0000126 AC: 1 AN: 79672

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 34574

Gnomad4 NFE exome AF: 0.0000148 AC: 16 AN: 1083722

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.0147 AC: 0.0146663 AN: 0.0146663

Gnomad4 AMR AF: 0.00131 AC: 0.00130651 AN: 0.00130651

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00237 AC: 0.00236518 AN: 0.00236518

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 v4.3

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
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
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

Publications

LitVar

Other links and lift over

dbSNP: rs8187717; hg19: chr6-160769797;