rs17001258

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001379110.1(SLC9A6):c.744-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,208,872 control chromosomes in the GnomAD database, including 69 homozygotes. There are 973 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 33 hom., 489 hem., cov: 23)

Exomes 𝑓: 0.0018 ( 36 hom. 484 hem. )

Consequence

SLC9A6
NM_001379110.1 splice_region, intron

Scores

Splicing: ADA: 0.0002719

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.32

Publications

2 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant X-136010436-C-T is Benign according to our data. Variant chrX-136010436-C-T is described in ClinVar as Benign. ClinVar VariationId is 139201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.744-6C>T		splice_region_variant, intron_variant	Intron 7 of 17	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC9A6	ENST00000630721.3 link	c.744-6C>T	splice_region_variant, intron_variant	Intron 7 of 17	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8 link	c.900-6C>T	splice_region_variant, intron_variant	Intron 6 of 15	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7 link	c.804-6C>T	splice_region_variant, intron_variant	Intron 6 of 15	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6 link	c.744-6C>T	splice_region_variant, intron_variant	Intron 7 of 16	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

1913

AN:

111818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00932

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:

0.000113

Gnomad OTH

AF:

0.00864

GnomAD2 exomes

AF:

0.00498

AC:

913

AN:

183393

AF XY:

0.00329

show subpopulations

Gnomad AFR exome

AF:

0.0625

Gnomad AMR exome

AF:

0.00273

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000610

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00181

AC:

1990

AN:

1097005

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

484

AN XY:

362397

show subpopulations

African (AFR)

AF:

0.0616

AC:

1625

AN:

26371

American (AMR)

AF:

0.00378

AC:

133

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19375

East Asian (EAS)

AF:

0.00

AC:

AN:

30191

South Asian (SAS)

AF:

0.0000924

AC:

AN:

54110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40472

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000416

AC:

AN:

841101

Other (OTH)

AF:

0.00406

AC:

187

AN:

46044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

145

217

290

362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.0171

AC:

1916

AN:

111867

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

489

AN XY:

34059

show subpopulations

African (AFR)

AF:

0.0585

AC:

1798

AN:

30721

American (AMR)

AF:

0.00940

AC:

AN:

10532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3586

South Asian (SAS)

AF:

0.00

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53257

Other (OTH)

AF:

0.00854

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00827

Hom.:

242

Bravo

AF:

0.0199

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 10, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Christianson syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.6

(source)

DANN

Benign

0.83

PhyloP100

1.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over