6-160242388-T-G

Variant names:

• chr6-160242388-T-G
• rs8177517
• NM_003058.4:c.1294A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003058.4(SLC22A2):​c.1294A>C​(p.Lys432Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,591,318 control chromosomes in the GnomAD database, including 36 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 0.0076 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (22 hom.)
• Consequence: SLC22A2 NM_003058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.92
• Publications: 39 publications found

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) 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. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036082268).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00756 (1151/152320) while in subpopulation AFR AF = 0.0258 (1072/41550). AF 95% confidence interval is 0.0245. There are 14 homozygotes in GnomAd4. There are 521 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003058.4. 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
	SLC22A2	NM_003058.4	MANE Select	c.1294A>C	p.Lys432Gln	missense	Exon 8 of 11	NP_003049.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.1294A>C	p.Lys432Gln	missense	Exon 8 of 11	ENSP00000355920.3
	SLC22A2	ENST00000486916.5	TSL:3	n.333A>C		non_coding_transcript_exon	Exon 3 of 6
	SLC22A2	ENST00000491092.1	TSL:5	n.1191A>C		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes AF: 0.00756 AC: 1150 AN: 152202 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00236 AC: 592 AN: 251024 AF XY: 0.00200

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000441

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00106 AC: 1521 AN: 1438998 Hom.: 22 Cov.: 26 AF XY: 0.00103 AC XY: 740 AN XY: 717510

African (AFR) AF: 0.0275 AC: 908 AN: 32970

American (AMR) AF: 0.00146 AC: 65 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39614

South Asian (SAS) AF: 0.00191 AC: 164 AN: 85822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00856 AC: 49 AN: 5726

European-Non Finnish (NFE) AF: 0.000208 AC: 227 AN: 1091168

Other (OTH) AF: 0.00176 AC: 105 AN: 59614

GnomAD4 genome AF: 0.00756 AC: 1151 AN: 152320 Hom.: 14 Cov.: 32 AF XY: 0.00699 AC XY: 521 AN XY: 74494

African (AFR) AF: 0.0258 AC: 1072 AN: 41550

American (AMR) AF: 0.00216 AC: 33 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

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: 0.000367 AC: 25 AN: 68032

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00335 Hom.: 15

Bravo AF: 0.00823

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00285 AC: 346

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.22
Sift	Benign	0.23	T
Sift4G	Benign	0.34	T
Polyphen		0.12	B
Vest4		0.25
MVP		0.58
MPC		0.10
ClinPred		0.061	T
GERP RS		5.1
Varity_R		0.35
gMVP		0.77
Mutation Taster		=92/8	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: rs8177517; hg19: chr6-160663420;