chrX-135985684-AG-A

Variant names:

• chrX-135985684-AG-A
• rs587784398
• NM_001379110.1:c.27delG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001379110.1(SLC9A6):​c.27delG​(p.Lys9AsnfsTer46) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: SLC9A6 NM_001379110.1 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.20
• Publications: 1 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 47 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-135985684-AG-A is Pathogenic according to our data. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135985684-AG-A is described in CliVar as Pathogenic. Clinvar id is 159931.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.27delG	p.Lys9AsnfsTer46	frameshift_variant	Exon 2 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.27delG	p.Lys9AsnfsTer46	frameshift_variant	Exon 2 of 18	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.183delG	p.Lys61AsnfsTer46	frameshift_variant	Exon 1 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.183delG	p.Lys61AsnfsTer46	frameshift_variant	Exon 1 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.27delG	p.Lys9AsnfsTer46	frameshift_variant	Exon 2 of 17	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Christianson syndrome Pathogenic:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=1/199	disease causing (ClinVar)

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: rs587784398; hg19: chrX-135067843;