Genetic Variant SLC22A6:p.Val471Met (chr11-62977338-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153276.3(SLC22A6):c.1411G>A(p.Val471Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SLC22A6
NM_153276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.266

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14622569).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153276.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A6	NM_153276.3	MANE Select	c.1411G>A	p.Val471Met	missense	Exon 9 of 10	NP_695008.1	Q4U2R8-2
SLC22A6	NM_004790.5		c.1411G>A	p.Val471Met	missense	Exon 9 of 10	NP_004781.2
SLC22A6	NM_153278.3		c.1362-83G>A		intron	N/A	NP_695010.1	Q4U2R8-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A6	ENST00000360421.9	TSL:1 MANE Select	c.1411G>A	p.Val471Met	missense	Exon 9 of 10	ENSP00000353597.4	Q4U2R8-2
SLC22A6	ENST00000377871.7	TSL:1	c.1411G>A	p.Val471Met	missense	Exon 9 of 10	ENSP00000367102.3	Q4U2R8-1
SLC22A6	ENST00000421062.2	TSL:1	c.1362-83G>A		intron	N/A	ENSP00000404441.2	Q4U2R8-4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000400

AC:

AN:

249988

AF XY:

0.0000591

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000478

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1460946

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726806

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52556

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000459

AC:

AN:

1111960

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.79

M_CAP

Benign

0.025

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.29

PhyloP100

0.27

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

REVEL

Benign

0.10

Sift

Benign

0.14

Sift4G

Benign

0.20

Polyphen

0.21

Vest4

0.14

MutPred

0.54

Loss of catalytic residue at V471 (P = 0.0218)

MVP

0.68

MPC

0.21

ClinPred

0.093

GERP RS

1.7

Varity_R

0.068

gMVP

0.61

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over