rs796053290

Variant names:

• chrX-135998094-CTTTAT-C
• rs796053290
• NM_001379110.1:c.370-9_370-5delTTTTA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PP1_Moderate PM2_Supporting PS4_Supporting PS3 PS2

This summary comes from the ClinGen Evidence Repository: The c.430-9_430-5del variant in SLC9A6 occurs in the de novo state (biological parentage confirmed) in an individual with delayed motor milestones and hypotonia (Baylor Genetics internal database)(PS2). RNA study has shown that this variant impacts splicing (PMID 27256868) (PS3). This variant has been reported to segregate in four informative meioses (PMID 27256868)(PP1_moderate). The c.430-9_430-5del variant in SLC9A6 has been observed in 2 unrelated families with Christianson syndrome (PMID 27256868, Baylor Genetics internal database) (PS4_supporting). The c.430-9_430-5del variant in SLC9A6 is absent from gnomAD (PM2_supporting). In summary The c.430-9_430-5del variant in SLC9A6 is classified as pathogenic for Christianson syndrome based on the ACMG/AMP criteria (PS2, PS3, PP1_moderate, PS4_supporting, PM2_supporting). LINK:https://erepo.genome.network/evrepo/ui/classification/CA318538/MONDO:0010278/016

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC9A6 NM_001379110.1 splice_region, intron
• Clinical Significance: Pathogenic reviewed by expert panel P:6 U:1
• Conservation: PhyloP100: 3.11
• Publications: 2 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, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PS2: For more information check the summary or visit ClinGen Evidence Repository.
• PS3: For more information check the summary or visit ClinGen Evidence Repository.
• PS4: For more information check the summary or visit ClinGen Evidence Repository.
• PM2: For more information check the summary or visit ClinGen Evidence Repository.
• PP1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379110.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	NM_001379110.1	MANE Select	c.370-9_370-5delTTTTA		splice_region intron	N/A	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.526-9_526-5delTTTTA		splice_region intron	N/A	NP_001425671.1
	SLC9A6	NM_001042537.2		c.526-9_526-5delTTTTA		splice_region intron	N/A	NP_001036002.1	Q92581-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.370-13_370-9delTTTAT		intron	N/A	ENSP00000487486.2	A0A0D9SGH0
	SLC9A6	ENST00000370695.8	TSL:1	c.526-13_526-9delTTTAT		intron	N/A	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.430-13_430-9delTTTAT		intron	N/A	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
4	-	-	Christianson syndrome (4)
1	-	-	Inborn genetic diseases (1)
1	-	-	Intellectual disability (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=20/80	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs796053290; hg19: chrX-135080253;