Genetic Variant SLC22A6:p.Arg50His (chr11-62984542-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153276.3(SLC22A6):c.149G>A(p.Arg50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,613,590 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.019 ( 84 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 78 hom. )

Consequence

SLC22A6
NM_153276.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.978

Publications

35 publications found

Variant links:

Genes affected

SLC22A6 (HGNC:10970): (solute carrier family 22 member 6) The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SLC22A6 links:

ENSG00000301851 (HGNC:):

ENSG00000301851 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0030465722).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A6	NM_153276.3 link	c.149G>A	p.Arg50His	missense_variant	Exon 1 of 10	ENST00000360421.9	NP_695008.1	Q4U2R8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A6	ENST00000360421.9 link	c.149G>A	p.Arg50His	missense_variant	Exon 1 of 10	1	NM_153276.3	ENSP00000353597.4		Q4U2R8-2

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2821

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00487

AC:

1202

AN:

246760

AF XY:

0.00355

show subpopulations

Gnomad AFR exome

AF:

0.0680

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00200

AC:

2929

AN:

1461366

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1247

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.0680

AC:

2277

AN:

33476

American (AMR)

AF:

0.00311

AC:

139

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39692

South Asian (SAS)

AF:

0.000128

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53202

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000225

AC:

250

AN:

1111820

Other (OTH)

AF:

0.00383

AC:

231

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

181

362

543

724

905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0186

AC:

2831

AN:

152224

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1347

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0645

AC:

2677

AN:

41532

American (AMR)

AF:

0.00654

AC:

100

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

67996

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

139

278

418

557

696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.0213

ESP6500AA

AF:

0.0654

AC:

288

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00583

AC:

708

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

.;T;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.65

T;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;M;M;M

PhyloP100

0.98

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.024

D;D;T;D

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.38

B;B;B;B

Vest4

0.12

MVP

0.59

MPC

0.69

ClinPred

0.019

GERP RS

2.8

PromoterAI

0.0028

Neutral

(source)

Varity_R

0.085

gMVP

0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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11-62984542-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over