Genetic Variant SLC9A9:c.*444C>A (chr3-143266258-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_173653.4(SLC9A9):c.*444C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 605,000 control chromosomes in the GnomAD database, including 88,437 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 0.53 ( 22568 hom., cov: 32)

Exomes 𝑓: 0.52 ( 65869 hom. )

Consequence

SLC9A9
NM_173653.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.274

Publications

9 publications found

Variant links:

Genes affected

SLC9A9 (HGNC:20653): (solute carrier family 9 member A9) This gene encodes a sodium/proton exchanger that is a member of the solute carrier 9 protein family. The encoded protein localizes the to the late recycling endosomes and may play an important role in maintaining cation homeostasis. Mutations in this gene are associated with autism susceptibility 16 and attention-deficit/hyperactivity disorder. [provided by RefSeq, Mar 2012]

SLC9A9 Gene-Disease associations (from GenCC):

autism, susceptibility to, 16
Inheritance: AD Classification: LIMITED Submitted by: G2P, PanelApp Australia
autism spectrum disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SLC9A9 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173653.4. 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
	SLC9A9	NM_173653.4	MANE Select	c.*444C>A		3_prime_UTR	Exon 16 of 16	NP_775924.1	Q8IVB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A9	ENST00000316549.11	TSL:1 MANE Select	c.*444C>A		3_prime_UTR	Exon 16 of 16	ENSP00000320246.6	Q8IVB4
	SLC9A9	ENST00000900956.1		c.*444C>A		3_prime_UTR	Exon 13 of 13	ENSP00000571015.1

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81102

AN:

151888

Hom.:

22555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.562

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.667

Gnomad EAS

AF:

0.0873

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.514

GnomAD4 exome

AF:

0.521

AC:

235919

AN:

452994

Hom.:

65869

Cov.:

AF XY:

0.520

AC XY:

124650

AN XY:

239902

show subpopulations

African (AFR)

AF:

0.555

AC:

6917

AN:

12466

American (AMR)

AF:

0.383

AC:

7355

AN:

19208

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

9350

AN:

14058

East Asian (EAS)

AF:

0.0826

AC:

2535

AN:

30694

South Asian (SAS)

AF:

0.465

AC:

20825

AN:

44806

European-Finnish (FIN)

AF:

0.458

AC:

13601

AN:

29720

Middle Eastern (MID)

AF:

0.524

AC:

1533

AN:

2924

European-Non Finnish (NFE)

AF:

0.586

AC:

159772

AN:

272876

Other (OTH)

AF:

0.535

AC:

14031

AN:

26242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

5131

10262

15394

20525

25656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.534

AC:

81147

AN:

152006

Hom.:

22568

Cov.:

AF XY:

0.521

AC XY:

38750

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.562

AC:

23295

AN:

41466

American (AMR)

AF:

0.436

AC:

6669

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

2313

AN:

3470

East Asian (EAS)

AF:

0.0873

AC:

451

AN:

5164

South Asian (SAS)

AF:

0.437

AC:

2103

AN:

4814

European-Finnish (FIN)

AF:

0.422

AC:

4450

AN:

10534

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.591

AC:

40147

AN:

67950

Other (OTH)

AF:

0.511

AC:

1080

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1912

3824

5737

7649

9561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.565

Hom.:

44202

Bravo

AF:

0.531

Asia WGS

AF:

0.272

AC:

948

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.39

PhyloP100

0.27

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