ENST00000370695.8:c.153A>G

Variant names:

• chrX-135985655-A-G
• rs782090744
• ENST00000370695.8:c.153A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Arg51= variant in SLC9A6 is 0.058% in South Asian sub population 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). In summary, the p.Arg51= variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA10524601/MONDO:0010278/016

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000025 (0 hom. 15 hem.)
• Consequence: SLC9A6 ENST00000370695.8 synonymous
• Clinical Significance: Benign reviewed by expert panel B:3
• Conservation: PhyloP100: 0.606
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.-4A>G		5_prime_UTR_variant	Exon 2 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000370695.8	c.153A>G	p.Arg51Arg	synonymous_variant	Exon 1 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.153A>G	p.Arg51Arg	synonymous_variant	Exon 1 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000630721.3	c.-4A>G		5_prime_UTR_variant	Exon 2 of 18	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370701.6	c.-4A>G		5_prime_UTR_variant	Exon 2 of 17	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 4 AN: 111600 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000601 AC: 11 AN: 183014 AF XY: 0.0000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000255 AC: 28 AN: 1098148 Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 15 AN XY: 363548

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.000499 AC: 27 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842076

Other (OTH) AF: 0.00 AC: 0 AN: 46089

GnomAD4 genome AF: 0.0000358 AC: 4 AN: 111648 Hom.: 0 Cov.: 22 AF XY: 0.0000295 AC XY: 1 AN XY: 33846

African (AFR) AF: 0.00 AC: 0 AN: 30782

American (AMR) AF: 0.00 AC: 0 AN: 10674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3496

South Asian (SAS) AF: 0.00151 AC: 4 AN: 2655

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52979

Other (OTH) AF: 0.00 AC: 0 AN: 1527

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: reviewed by expert panel

Submissions by phenotype

Christianson syndrome Benign:2

Mar 26, 2021

ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

The allele frequency of the p.Arg51= variant in SLC9A6 is 0.058% in South Asian sub population 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). In summary, the p.Arg51= variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BA1). -

Oct 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Sep 22, 2016

GeneDx

Significance: Likely 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		0.61
PromoterAI		0.047	Neutral
Mutation Taster		=293/7	polymorphism

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

Other links and lift over

dbSNP: rs782090744; hg19: chrX-135067814;