Variant rs180727016 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001379110.1(SLC9A6):c.1460+4A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,193,640 control chromosomes in the GnomAD database, including 6 homozygotes. There are 1,255 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., 85 hem., cov: 23)

Exomes 𝑓: 0.0032 ( 6 hom. 1170 hem. )

Consequence

SLC9A6
NM_001379110.1 splice_donor_region, intron

Scores

Splicing: ADA: 0.009188

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.991

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant X-136024487-A-G is Benign according to our data. Variant chrX-136024487-A-G is described in ClinVar as [Benign]. Clinvar id is 95376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136024487-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 85 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 linkuse as main transcript	c.1460+4A>G		splice_donor_region_variant, intron_variant		ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3 linkuse as main transcript	c.1460+4A>G		splice_donor_region_variant, intron_variant		4	NM_001379110.1	ENSP00000487486

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

259

AN:

111793

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

AN XY:

33961

show subpopulations

Gnomad AFR

AF:

0.000357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000747

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00327

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00261

AC:

478

AN:

183114

Hom.:

AF XY:

0.00293

AC XY:

198

AN XY:

67600

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00132

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00316

AC:

3423

AN:

1081795

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

1170

AN XY:

347829

show subpopulations

Gnomad4 AFR exome

AF:

0.000115

Gnomad4 AMR exome

AF:

0.000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000664

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00341

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00232

AC:

259

AN:

111845

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

AN XY:

34023

show subpopulations

Gnomad4 AFR

AF:

0.000356

Gnomad4 AMR

AF:

0.000477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000750

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.00327

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00136

EpiCase

AF:

0.00235

EpiControl

AF:

0.00339

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 04, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 11, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 10, 2015	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Christianson syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2019

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. -

SLC9A6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2019

This variant is classified as 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

-0.64

CADD

Benign

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0092

dbscSNV1_RF

Benign

0.26

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