Genetic Variant SLC12A7:p.Val1014Ile (chr5-1053469-C-T) – 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_006598.3(SLC12A7):c.3040G>A(p.Val1014Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000057 in 1,613,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

SLC12A7
NM_006598.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Publications

1 publications found

Variant links:

Genes affected

SLC12A7 (HGNC:10915): (solute carrier family 12 member 7) Enables protein kinase binding activity. Predicted to be involved in several processes, including cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC12A7 Gene-Disease associations (from GenCC):

renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

SLC12A7 links:

Genome browser will be placed here

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=0.3755089).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006598.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A7	NM_006598.3	MANE Select	c.3040G>A	p.Val1014Ile	missense	Exon 23 of 24	NP_006589.2	Q9Y666-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC12A7	ENST00000264930.10	TSL:1 MANE Select	c.3040G>A	p.Val1014Ile	missense	Exon 23 of 24	ENSP00000264930.5	Q9Y666-1
SLC12A7	ENST00000634447.1	TSL:5	c.2755G>A	p.Val919Ile	missense	Exon 22 of 23	ENSP00000489285.1	A0A0U1RR18
SLC12A7	ENST00000945163.1		c.3157G>A	p.Val1053Ile	missense	Exon 25 of 26	ENSP00000615222.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000440

AC:

AN:

250100

AF XY:

0.0000369

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000588

AC:

AN:

1461362

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000639

AC:

AN:

1111932

Other (OTH)

AF:

0.000166

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000394

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

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:

0.0000394

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

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

0.21

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.062

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.6

PhyloP100

6.9

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.87

REVEL

Benign

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.033

Polyphen

0.60

Vest4

0.52

MVP

0.36

MPC

0.64

ClinPred

0.29

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.39

gMVP

0.32

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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