rs2307131

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379110.1(SLC9A6):c.1689C>T(p.Ser563Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 1,208,581 control chromosomes in the GnomAD database, including 571 homozygotes. There are 14,130 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 0.030 ( 43 hom., 1014 hem., cov: 23)

Exomes 𝑓: 0.034 ( 528 hom. 13116 hem. )

Consequence

SLC9A6
NM_001379110.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.49

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant X-136040103-C-T is Benign according to our data. Variant chrX-136040103-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 139209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136040103-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.1689C>T	p.Ser563Ser	synonymous_variant	Exon 17 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC9A6	ENST00000630721.3 link	c.1689C>T	p.Ser563Ser	synonymous_variant	Exon 17 of 18	4	NM_001379110.1	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695.8 link	c.1755C>T	p.Ser585Ser	synonymous_variant	Exon 15 of 16	1		ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7 link	c.1659C>T	p.Ser553Ser	synonymous_variant	Exon 15 of 16	1		ENSP00000359732.3	Q92581-1
SLC9A6	ENST00000370701.6 link	c.1599C>T	p.Ser533Ser	synonymous_variant	Exon 16 of 17	1		ENSP00000359735.1	Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.0300

AC:

3362

AN:

112124

Hom.:

Cov.:

AF XY:

0.0295

AC XY:

1012

AN XY:

34274

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00979

Gnomad ASJ

AF:

0.0241

Gnomad EAS

AF:

0.0794

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.0273

Gnomad OTH

AF:

0.0212

GnomAD3 exomes

AF:

0.0359

AC:

6490

AN:

180631

Hom.:

AF XY:

0.0402

AC XY:

2630

AN XY:

65353

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.00763

Gnomad ASJ exome

AF:

0.0254

Gnomad EAS exome

AF:

0.0685

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0326

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0338

AC:

37086

AN:

1096406

Hom.:

528

Cov.:

AF XY:

0.0362

AC XY:

13116

AN XY:

361964

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00788

Gnomad4 ASJ exome

AF:

0.0268

Gnomad4 EAS exome

AF:

0.0810

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.0333

Gnomad4 NFE exome

AF:

0.0291

Gnomad4 OTH exome

AF:

0.0323

GnomAD4 genome

AF:

0.0300

AC:

3365

AN:

112175

Hom.:

Cov.:

AF XY:

0.0295

AC XY:

1014

AN XY:

34335

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.0241

Gnomad4 EAS

AF:

0.0792

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0288

Gnomad4 NFE

AF:

0.0273

Gnomad4 OTH

AF:

0.0216

Alfa

AF:

0.0291

Hom.:

392

Bravo

AF:

0.0278

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Feb 21, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 06, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 02, 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. -

Inborn genetic diseases

Benign:1

Sep 25, 2015

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

-0.62

CADD

Benign

0.063

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over