Genetic Variant SLC12A9:c.317-120T>C (chr7-100855586-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020246.4(SLC12A9):c.317-120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,349,510 control chromosomes in the GnomAD database, including 21,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1795 hom., cov: 32)

Exomes 𝑓: 0.17 ( 19589 hom. )

Consequence

SLC12A9
NM_020246.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.572

Publications

56 publications found

Variant links:

Genes affected

SLC12A9 (HGNC:17435): (solute carrier family 12 member 9) Predicted to enable potassium:chloride symporter activity. Predicted to be involved in cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SLC12A9 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

SLC12A9 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 (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A9	NM_020246.4 link	c.317-120T>C		intron_variant	Intron 3 of 13	ENST00000354161.8	NP_064631.2	Q9BXP2-1Q9H7I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A9	ENST00000354161.8 link	c.317-120T>C		intron_variant	Intron 3 of 13	1	NM_020246.4	ENSP00000275730.4		Q9BXP2-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20876

AN:

152142

Hom.:

1800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0514

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.0351

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.174

AC:

208702

AN:

1197250

Hom.:

19589

Cov.:

AF XY:

0.173

AC XY:

104136

AN XY:

601366

show subpopulations

African (AFR)

AF:

0.0488

AC:

1370

AN:

28046

American (AMR)

AF:

0.126

AC:

4944

AN:

39348

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

4639

AN:

21528

East Asian (EAS)

AF:

0.0273

AC:

1038

AN:

38022

South Asian (SAS)

AF:

0.130

AC:

9674

AN:

74222

European-Finnish (FIN)

AF:

0.222

AC:

10347

AN:

46672

Middle Eastern (MID)

AF:

0.203

AC:

1038

AN:

5124

European-Non Finnish (NFE)

AF:

0.187

AC:

167245

AN:

892816

Other (OTH)

AF:

0.163

AC:

8407

AN:

51472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8322

16645

24967

33290

41612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5338

10676

16014

21352

26690

<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:

0.137

AC:

20868

AN:

152260

Hom.:

1795

Cov.:

AF XY:

0.136

AC XY:

10110

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0514

AC:

2135

AN:

41562

American (AMR)

AF:

0.111

AC:

1699

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

727

AN:

3472

East Asian (EAS)

AF:

0.0346

AC:

179

AN:

5178

South Asian (SAS)

AF:

0.116

AC:

558

AN:

4830

European-Finnish (FIN)

AF:

0.219

AC:

2321

AN:

10598

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.187

AC:

12722

AN:

67998

Other (OTH)

AF:

0.143

AC:

301

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

903

1806

2710

3613

4516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.169

Hom.:

8113

Bravo

AF:

0.126

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.8

(source)

DANN

Benign

0.63

PhyloP100

0.57

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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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