X-135985527-G-T

Position:

chrX-135985527-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP4

This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Ala9Ser variant in SLC9A6 is 0.307% in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). Computational analysis prediction tools suggest that the p.Ala9Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Ala9Ser variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BA1, BP4). LINK:https://erepo.genome.network/evrepo/ui/classification/CA295170/MONDO:0010278/016

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., 107 hem., cov: 22)

Exomes 𝑓: 0.0045 ( 9 hom. 1447 hem. )

Consequence

SLC9A6
ENST00000370695.8 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:10

Conservation

PhyloP100: 2.12

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 -9 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 linkuse as main transcript	c.-57+50G>T		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.-57+50G>T		intron_variant		4	NM_001379110.1	ENSP00000487486

Frequencies

GnomAD3 genomes

AF:

0.00339

AC:

377

AN:

111153

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

107

AN XY:

33375

show subpopulations

Gnomad AFR

AF:

0.000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000377

Gnomad FIN

AF:

0.00603

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.00571

Gnomad OTH

AF:

0.00469

GnomAD3 exomes

AF:

0.00289

AC:

250

AN:

86554

Hom.:

AF XY:

0.00326

AC XY:

AN XY:

14414

show subpopulations

Gnomad AFR exome

AF:

0.000776

Gnomad AMR exome

AF:

0.000874

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00779

Gnomad NFE exome

AF:

0.00480

Gnomad OTH exome

AF:

0.00445

GnomAD4 exome

AF:

0.00452

AC:

4606

AN:

1019726

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

1447

AN XY:

320406

show subpopulations

Gnomad4 AFR exome

AF:

0.000549

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.000126

Gnomad4 EAS exome

AF:

0.0000365

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00828

Gnomad4 NFE exome

AF:

0.00512

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00339

AC:

377

AN:

111193

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

107

AN XY:

33427

show subpopulations

Gnomad4 AFR

AF:

0.000651

Gnomad4 AMR

AF:

0.00103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000378

Gnomad4 FIN

AF:

0.00603

Gnomad4 NFE

AF:

0.00571

Gnomad4 OTH

AF:

0.00463

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.00278

ExAC

AF:

0.00263

AC:

297

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 21, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2016	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 23, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 18, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 13, 2018	- -

Christianson syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, reviewed by expert panel	curation	ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	Mar 26, 2021	The allele frequency of the p.Ala9Ser variant in SLC9A6 is 0.307% in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). Computational analysis prediction tools suggest that the p.Ala9Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Ala9Ser variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BA1, BP4). -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 18, 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

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.095

.;T

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.037

Sift

Benign

0.11

T;T

Sift4G

Benign

0.75

T;T

Polyphen

0.0

B;B

Vest4

0.20

MVP

0.15

MPC

0.95

ClinPred

0.0036

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.068

gMVP

0.25

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

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