Genetic Variant NM_153276.3:c.1408A>G (chr11-62977341-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_153276.3(SLC22A6):c.1408A>G(p.Ile470Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC22A6
NM_153276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2920224).

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.1408A>G	p.Ile470Val	missense	Exon 9 of 10	NP_695008.1	Q4U2R8-2
SLC22A6	NM_004790.5		c.1408A>G	p.Ile470Val	missense	Exon 9 of 10	NP_004781.2
SLC22A6	NM_153278.3		c.1362-86A>G		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.1408A>G	p.Ile470Val	missense	Exon 9 of 10	ENSP00000353597.4	Q4U2R8-2
SLC22A6	ENST00000377871.7	TSL:1	c.1408A>G	p.Ile470Val	missense	Exon 9 of 10	ENSP00000367102.3	Q4U2R8-1
SLC22A6	ENST00000421062.2	TSL:1	c.1362-86A>G		intron	N/A	ENSP00000404441.2	Q4U2R8-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000800

AC:

AN:

249940

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111954

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

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

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

Cov.:

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

0.096

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.022

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.6

PhyloP100

4.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.50

REVEL

Benign

0.26

Sift

Uncertain

0.011

Sift4G

Benign

0.37

Polyphen

0.54

Vest4

0.36

MutPred

0.54

Gain of disorder (P = 0.1137)

MVP

0.74

MPC

0.60

ClinPred

0.79

GERP RS

4.8

Varity_R

0.22

gMVP

0.55

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over