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):

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

SLC12A9 links:

Genome browser will be placed here

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC12A9	NM_020246.4	MANE Select	c.317-120T>C	intron	N/A	NP_064631.2
SLC12A9	NM_001363493.2		c.317-120T>C	intron	N/A	NP_001350422.1	Q9BXP2-1
SLC12A9	NM_001363494.1		c.20-1282T>C	intron	N/A	NP_001350423.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC12A9	ENST00000354161.8	TSL:1 MANE Select	c.317-120T>C	intron	N/A	ENSP00000275730.4	Q9BXP2-1
SLC12A9	ENST00000415287.5	TSL:1	c.181+1208T>C	intron	N/A	ENSP00000413796.1	Q9BXP2-2
SLC12A9	ENST00000971215.1		c.317-120T>C	intron	N/A	ENSP00000641274.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over