rs142049079

Variant names:

• chrX-136013386-A-C
• rs142049079
• NM_001379110.1:c.1029A>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001379110.1(SLC9A6):​c.1029A>C​(p.Ala343Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,206,366 control chromosomes in the GnomAD database, including 22 homozygotes. There are 2,039 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., 120 hem., cov: 24)
  • Exomes 𝑓: 0.0052 (20 hom. 1919 hem.)
• Consequence: SLC9A6 NM_001379110.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.409

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-136013386-A-C is Benign according to our data. Variant chrX-136013386-A-C is described in ClinVar as [Benign]. Clinvar id is 139203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136013386-A-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.409 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00407 (456/112015) while in subpopulation SAS AF= 0.00743 (20/2690). AF 95% confidence interval is 0.00603. There are 2 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.1029A>C	p.Ala343Ala	synonymous_variant	Exon 10 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.1029A>C	p.Ala343Ala	synonymous_variant	Exon 10 of 18	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.1185A>C	p.Ala395Ala	synonymous_variant	Exon 9 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.1089A>C	p.Ala363Ala	synonymous_variant	Exon 9 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.1029A>C	p.Ala343Ala	synonymous_variant	Exon 10 of 17	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 456 AN: 111963 Hom.: 2 Cov.: 24 AF XY: 0.00352 AC XY: 120 AN XY: 34123

Gnomad AFR AF: 0.000519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00200

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.000279

Gnomad SAS AF: 0.00741

Gnomad FIN AF: 0.000496

Gnomad MID AF: 0.00840

Gnomad NFE AF: 0.00660

Gnomad OTH AF: 0.00461

GnomAD3 exomes AF: 0.00463 AC: 849 AN: 183404 Hom.: 2 AF XY: 0.00532 AC XY: 361 AN XY: 67868

Gnomad AFR exome AF: 0.00106

Gnomad AMR exome AF: 0.00164

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.0000722

Gnomad SAS exome AF: 0.00677

Gnomad FIN exome AF: 0.000562

Gnomad NFE exome AF: 0.00653

Gnomad OTH exome AF: 0.00640

GnomAD4 exome AF: 0.00515 AC: 5639 AN: 1094351 Hom.: 20 Cov.: 29 AF XY: 0.00533 AC XY: 1919 AN XY: 359893

Gnomad4 AFR exome AF: 0.000987

Gnomad4 AMR exome AF: 0.00193

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00635

Gnomad4 FIN exome AF: 0.000642

Gnomad4 NFE exome AF: 0.00554

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.00407 AC: 456 AN: 112015 Hom.: 2 Cov.: 24 AF XY: 0.00351 AC XY: 120 AN XY: 34185

Gnomad4 AFR AF: 0.000518

Gnomad4 AMR AF: 0.00199

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.000280

Gnomad4 SAS AF: 0.00743

Gnomad4 FIN AF: 0.000496

Gnomad4 NFE AF: 0.00660

Gnomad4 OTH AF: 0.00455

Alfa AF: 0.00736 Hom.: 54

Bravo AF: 0.00351

EpiCase AF: 0.00611

EpiControl AF: 0.00877

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Oct 15, 2015

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 12, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 30, 2016

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 14, 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. -

Christianson syndrome Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 03, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Jan 25, 2016

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: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.7
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs142049079; hg19: chrX-135095545;