X-135998508-T-C

Variant names:

Variant summary

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

-21

BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001379110.1(SLC9A6):c.474T>C(p.Ser158Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,176,895 control chromosomes in the GnomAD database, including 17 homozygotes. There are 311 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., 153 hem., cov: 22)

Exomes 𝑓: 0.00060 ( 11 hom. 158 hem. )

Consequence

SLC9A6
NM_001379110.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.208

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=-0.58).

BP6

Variant X-135998508-T-C is Benign according to our data. Variant chrX-135998508-T-C is described in ClinVar as [Benign]. Clinvar id is 139200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.208 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00616 (681/110496) while in subpopulation AFR AF = 0.0214 (651/30408). AF 95% confidence interval is 0.02. There are 6 homozygotes in GnomAd4. There are 153 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.474T>C	p.Ser158Ser	synonymous_variant	Exon 5 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC9A6	ENST00000630721.3 link	c.474T>C	p.Ser158Ser	synonymous_variant	Exon 5 of 18	4	NM_001379110.1	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695.8 link	c.630T>C	p.Ser210Ser	synonymous_variant	Exon 4 of 16	1		ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7 link	c.534T>C	p.Ser178Ser	synonymous_variant	Exon 4 of 16	1		ENSP00000359732.3	Q92581-1
SLC9A6	ENST00000370701.6 link	c.474T>C	p.Ser158Ser	synonymous_variant	Exon 5 of 17	1		ENSP00000359735.1	Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.00617

AC:

681

AN:

110451

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00252

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:

0.00

Gnomad OTH

AF:

0.00270

GnomAD2 exomes

AF:

0.00193

AC:

316

AN:

163836

AF XY:

0.000933

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000603

AC:

643

AN:

1066399

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

158

AN XY:

343139

show subpopulations

African (AFR)

AF:

0.0216

AC:

541

AN:

24998

American (AMR)

AF:

0.000925

AC:

AN:

30279

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18534

East Asian (EAS)

AF:

0.00

AC:

AN:

29465

South Asian (SAS)

AF:

0.0000429

AC:

AN:

46571

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39766

Middle Eastern (MID)

AF:

0.000749

AC:

AN:

4005

European-Non Finnish (NFE)

AF:

0.00000966

AC:

AN:

828091

Other (OTH)

AF:

0.00136

AC:

AN:

44690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00616

AC:

681

AN:

110496

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

153

AN XY:

32770

show subpopulations

African (AFR)

AF:

0.0214

AC:

651

AN:

30408

American (AMR)

AF:

0.00251

AC:

AN:

10347

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2630

East Asian (EAS)

AF:

0.00

AC:

AN:

3574

South Asian (SAS)

AF:

0.00

AC:

AN:

2609

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52775

Other (OTH)

AF:

0.00267

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

116

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:

0.0113

Hom.:

107

Bravo

AF:

0.00788

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 15, 2013

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. -

Mar 07, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Christianson syndrome

Benign:2

Jun 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

Oct 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

- -

SLC9A6-related disorder

Benign:1

Apr 02, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.7

(source)

DANN

Benign

0.43

PhyloP100

-0.21

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over