rs6654310

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379110.1(SLC9A6):c.1306+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,106,638 control chromosomes in the GnomAD database, including 1,438 homozygotes. There are 18,311 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 330 hom., 2395 hem., cov: 22)

Exomes 𝑓: 0.049 ( 1108 hom. 15916 hem. )

Consequence

SLC9A6
NM_001379110.1 splice_region, intron

Scores

Splicing: ADA: 0.00004423

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.200

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-136022705-G-A is Benign according to our data. Variant chrX-136022705-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.1306+8G>A		splice_region_variant, intron_variant	Intron 12 of 17	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC9A6	ENST00000630721.3 link	c.1306+8G>A	splice_region_variant, intron_variant	Intron 12 of 17	4	NM_001379110.1	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695.8 link	c.1462+8G>A	splice_region_variant, intron_variant	Intron 11 of 15	1		ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7 link	c.1366+8G>A	splice_region_variant, intron_variant	Intron 11 of 15	1		ENSP00000359732.3	Q92581-1
SLC9A6	ENST00000370701.6 link	c.1306+8G>A	splice_region_variant, intron_variant	Intron 12 of 16	1		ENSP00000359735.1	Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.0740

AC:

8260

AN:

111597

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0333

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.0793

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0378

Gnomad MID

AF:

0.0333

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0499

GnomAD2 exomes

AF:

0.0551

AC:

10038

AN:

182180

AF XY:

0.0568

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0376

Gnomad EAS exome

AF:

0.0688

Gnomad FIN exome

AF:

0.0408

Gnomad NFE exome

AF:

0.0368

Gnomad OTH exome

AF:

0.0491

GnomAD4 exome

AF:

0.0494

AC:

49177

AN:

994989

Hom.:

1108

Cov.:

AF XY:

0.0564

AC XY:

15916

AN XY:

282001

show subpopulations

African (AFR)

AF:

0.174

AC:

4252

AN:

24502

American (AMR)

AF:

0.0224

AC:

771

AN:

34494

Ashkenazi Jewish (ASJ)

AF:

0.0401

AC:

727

AN:

18150

East Asian (EAS)

AF:

0.0815

AC:

2328

AN:

28548

South Asian (SAS)

AF:

0.119

AC:

6163

AN:

51760

European-Finnish (FIN)

AF:

0.0423

AC:

1627

AN:

38426

Middle Eastern (MID)

AF:

0.0352

AC:

134

AN:

3811

European-Non Finnish (NFE)

AF:

0.0411

AC:

30955

AN:

753273

Other (OTH)

AF:

0.0528

AC:

2220

AN:

42025

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1377

2754

4130

5507

6884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1326

2652

3978

5304

6630

<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:

0.0741

AC:

8275

AN:

111649

Hom.:

330

Cov.:

AF XY:

0.0707

AC XY:

2395

AN XY:

33859

show subpopulations

African (AFR)

AF:

0.158

AC:

4841

AN:

30617

American (AMR)

AF:

0.0406

AC:

429

AN:

10558

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

AN:

2648

East Asian (EAS)

AF:

0.0790

AC:

281

AN:

3556

South Asian (SAS)

AF:

0.128

AC:

341

AN:

2663

European-Finnish (FIN)

AF:

0.0378

AC:

227

AN:

6002

Middle Eastern (MID)

AF:

0.0321

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0367

AC:

1953

AN:

53174

Other (OTH)

AF:

0.0499

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

263

525

788

1050

1313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0523

Hom.:

1086

Bravo

AF:

0.0790

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 21, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 02, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 22, 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. -

May 06, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 24, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Christianson syndrome

Benign:1

Feb 04, 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

-0.80

CADD

Benign

0.50

(source)

DANN

Benign

0.56

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.016

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