rs398122849

Variant names:

• chrX-136010553-GGGTGCTGCT-G
• rs398122849
• NM_001379110.1:c.856_864delGGTGCTGCT

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_001379110.1(SLC9A6):​c.856_864delGGTGCTGCT​(p.Gly286_Ala288del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC9A6 NM_001379110.1 conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.60
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001379110.1.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant X-136010553-GGGTGCTGCT-G is Pathogenic according to our data. Variant chrX-136010553-GGGTGCTGCT-G is described in ClinVar as Pathogenic. ClinVar VariationId is 29949.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.856_864delGGTGCTGCT	p.Gly286_Ala288del	conservative_inframe_deletion	Exon 8 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.856_864delGGTGCTGCT	p.Gly286_Ala288del	conservative_inframe_deletion	Exon 8 of 18	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.1012_1020delGGTGCTGCT	p.Gly338_Ala340del	conservative_inframe_deletion	Exon 7 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.916_924delGGTGCTGCT	p.Gly306_Ala308del	conservative_inframe_deletion	Exon 7 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.856_864delGGTGCTGCT	p.Gly286_Ala288del	conservative_inframe_deletion	Exon 8 of 17	1		ENSP00000359735.1

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Christianson syndrome Pathogenic:1

May 01, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6
Mutation Taster		=6/194	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs398122849; hg19: chrX-135092712;