rs188072063

Positions:

chrX-136040072-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001379110.1(SLC9A6):c.1662-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,197,139 control chromosomes in the GnomAD database, including 45 homozygotes. There are 4,024 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 0.0070 ( 4 hom., 221 hem., cov: 24)

Exomes 𝑓: 0.011 ( 41 hom. 3803 hem. )

Consequence

SLC9A6
NM_001379110.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006198

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

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

BP6

Variant X-136040072-G-A is Benign according to our data. Variant chrX-136040072-G-A is described in ClinVar as [Benign]. Clinvar id is 139208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136040072-G-A is described in Lovd as [Benign]. Variant chrX-136040072-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A6	NM_001379110.1 linkuse as main transcript	c.1662-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000630721.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A6	ENST00000630721.3 linkuse as main transcript	c.1662-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		4	NM_001379110.1

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

787

AN:

112050

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

221

AN XY:

34234

show subpopulations

Gnomad AFR

AF:

0.00120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00944

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00522

Gnomad FIN

AF:

0.00313

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00665

GnomAD3 exomes

AF:

0.00631

AC:

1124

AN:

178130

Hom.:

AF XY:

0.00647

AC XY:

408

AN XY:

63088

show subpopulations

Gnomad AFR exome

AF:

0.000703

Gnomad AMR exome

AF:

0.00265

Gnomad ASJ exome

AF:

0.000135

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.00404

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00704

GnomAD4 exome

AF:

0.0110

AC:

11910

AN:

1085033

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

3803

AN XY:

351625

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00365

Gnomad4 ASJ exome

AF:

0.000156

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00527

Gnomad4 FIN exome

AF:

0.00435

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.00957

GnomAD4 genome

AF:

0.00702

AC:

787

AN:

112106

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

221

AN XY:

34300

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00943

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00523

Gnomad4 FIN

AF:

0.00313

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00657

Alfa

AF:

0.00904

Hom.:

Bravo

AF:

0.00712

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 08, 2015	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2012	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. -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 17, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Christianson syndrome

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.027

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000062

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

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