dbSNP rs142161862: SLC9A6:p.Gln429Gln (chrX-136022678-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001379110.1(SLC9A6):c.1287A>G(p.Gln429Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,177,217 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000037 ( 0 hom. 12 hem. )

Consequence

SLC9A6
NM_001379110.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.69

Publications

1 publications found

Variant links:

Genes affected

SLC9A6 (HGNC:11079): (solute carrier family 9 member A6) This gene encodes a sodium-hydrogen exchanger that is amember of the solute carrier family 9. The encoded protein localizes to early and recycling endosomes and may be involved in regulating endosomal pH and volume. Defects in this gene are associated with X-linked syndromic cognitive disability, Christianson type. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

SLC9A6 Gene-Disease associations (from GenCC):

Christianson syndrome
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen

SLC9A6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-136022678-A-G is Benign according to our data. Variant chrX-136022678-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 207234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000626 (7/111879) while in subpopulation NFE AF = 0.000132 (7/53196). AF 95% confidence interval is 0.0000615. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379110.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC9A6	NM_001379110.1	MANE Select	c.1287A>G	p.Gln429Gln	synonymous	Exon 12 of 18	NP_001366039.1
SLC9A6	NM_001438742.1		c.1443A>G	p.Gln481Gln	synonymous	Exon 11 of 17	NP_001425671.1
SLC9A6	NM_001042537.2		c.1443A>G	p.Gln481Gln	synonymous	Exon 11 of 16	NP_001036002.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.1287A>G	p.Gln429Gln	synonymous	Exon 12 of 18	ENSP00000487486.2
SLC9A6	ENST00000370695.8	TSL:1	c.1443A>G	p.Gln481Gln	synonymous	Exon 11 of 16	ENSP00000359729.4
SLC9A6	ENST00000370698.7	TSL:1	c.1347A>G	p.Gln449Gln	synonymous	Exon 11 of 16	ENSP00000359732.3

Frequencies

GnomAD3 genomes

AF:

0.0000626

AC:

AN:

111879

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000491

AC:

AN:

183190

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000313

Gnomad NFE exome

AF:

0.0000489

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000366

AC:

AN:

1065338

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

334424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25711

American (AMR)

AF:

0.00

AC:

AN:

34794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18835

East Asian (EAS)

AF:

0.00

AC:

AN:

29289

South Asian (SAS)

AF:

0.00

AC:

AN:

53346

European-Finnish (FIN)

AF:

0.000102

AC:

AN:

39357

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4005

European-Non Finnish (NFE)

AF:

0.0000417

AC:

AN:

815404

Other (OTH)

AF:

0.0000224

AC:

AN:

44597

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000626

AC:

AN:

111879

Hom.:

Cov.:

AF XY:

0.0000587

AC XY:

AN XY:

34051

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30749

American (AMR)

AF:

0.00

AC:

AN:

10546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3587

South Asian (SAS)

AF:

0.00

AC:

AN:

2693

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6027

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

53196

Other (OTH)

AF:

0.00

AC:

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.00

Hom.:

Bravo

AF:

0.0000378

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 28, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC9A6: BP4, BP7, BS2

not specified

Benign:1

Jun 22, 2017

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Christianson syndrome

Benign:1

Nov 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.3

(source)

DANN

Benign

0.59

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism

(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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over