rs142049079

Variant names:

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.1029A>C(p.Ala343Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,206,366 control chromosomes in the GnomAD database, including 22 homozygotes. There are 2,039 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., 120 hem., cov: 24)

Exomes 𝑓: 0.0052 ( 20 hom. 1919 hem. )

Consequence

SLC9A6
NM_001379110.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.409

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=-0.53).

BP6

Variant X-136013386-A-C is Benign according to our data. Variant chrX-136013386-A-C is described in ClinVar as Benign. ClinVar VariationId is 139203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.409 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00407 (456/112015) while in subpopulation SAS AF = 0.00743 (20/2690). AF 95% confidence interval is 0.00603. There are 2 homozygotes in GnomAd4. There are 120 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.1029A>C	p.Ala343Ala	synonymous_variant	Exon 10 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC9A6	ENST00000630721.3 link	c.1029A>C	p.Ala343Ala	synonymous_variant	Exon 10 of 18	4	NM_001379110.1	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695.8 link	c.1185A>C	p.Ala395Ala	synonymous_variant	Exon 9 of 16	1		ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7 link	c.1089A>C	p.Ala363Ala	synonymous_variant	Exon 9 of 16	1		ENSP00000359732.3	Q92581-1
SLC9A6	ENST00000370701.6 link	c.1029A>C	p.Ala343Ala	synonymous_variant	Exon 10 of 17	1		ENSP00000359735.1	Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

456

AN:

111963

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000519

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00200

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00741

Gnomad FIN

AF:

0.000496

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.00660

Gnomad OTH

AF:

0.00461

GnomAD2 exomes

AF:

0.00463

AC:

849

AN:

183404

AF XY:

0.00532

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00164

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.0000722

Gnomad FIN exome

AF:

0.000562

Gnomad NFE exome

AF:

0.00653

Gnomad OTH exome

AF:

0.00640

GnomAD4 exome

AF:

0.00515

AC:

5639

AN:

1094351

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

1919

AN XY:

359893

show subpopulations

African (AFR)

AF:

0.000987

AC:

AN:

26330

American (AMR)

AF:

0.00193

AC:

AN:

35189

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

223

AN:

19347

East Asian (EAS)

AF:

0.00

AC:

AN:

30163

South Asian (SAS)

AF:

0.00635

AC:

343

AN:

54010

European-Finnish (FIN)

AF:

0.000642

AC:

AN:

40486

Middle Eastern (MID)

AF:

0.0152

AC:

AN:

4082

European-Non Finnish (NFE)

AF:

0.00554

AC:

4649

AN:

838777

Other (OTH)

AF:

0.00526

AC:

242

AN:

45967

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

168

336

505

673

841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<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:

0.00407

AC:

456

AN:

112015

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

120

AN XY:

34185

show subpopulations

African (AFR)

AF:

0.000518

AC:

AN:

30872

American (AMR)

AF:

0.00199

AC:

AN:

10534

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

2652

East Asian (EAS)

AF:

0.000280

AC:

AN:

3574

South Asian (SAS)

AF:

0.00743

AC:

AN:

2690

European-Finnish (FIN)

AF:

0.000496

AC:

AN:

6053

Middle Eastern (MID)

AF:

0.00922

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00660

AC:

351

AN:

53200

Other (OTH)

AF:

0.00455

AC:

AN:

1538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00736

Hom.:

Bravo

AF:

0.00351

EpiCase

AF:

0.00611

EpiControl

AF:

0.00877

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Oct 15, 2015

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 12, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 14, 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. -

Sep 30, 2016

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Christianson syndrome

Benign:2

Aug 03, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 25, 2016

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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.7

(source)

DANN

Benign

0.73

PhyloP100

0.41

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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