rs730882187

Variant names:

• chrX-135998188-AA-CC
• rs730882187
• NM_001379110.1:c.447+3_447+4delAAinsCC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_001379110.1(SLC9A6):​c.447+3_447+4delAAinsCC variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC9A6 NM_001379110.1 splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.14
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP5: Variant X-135998188-AA-CC is Pathogenic according to our data. Variant chrX-135998188-AA-CC is described in ClinVar as Pathogenic. ClinVar VariationId is 11478.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	NM_001379110.1	MANE Select	c.447+3_447+4delAAinsCC		splice_region intron	N/A	NP_001366039.1
	SLC9A6	NM_001438742.1		c.603+3_603+4delAAinsCC		splice_region intron	N/A	NP_001425671.1
	SLC9A6	NM_001042537.2		c.603+3_603+4delAAinsCC		splice_region intron	N/A	NP_001036002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.447+3_447+4delAAinsCC		splice_region intron	N/A	ENSP00000487486.2
	SLC9A6	ENST00000370695.8	TSL:1	c.603+3_603+4delAAinsCC		splice_region intron	N/A	ENSP00000359729.4
	SLC9A6	ENST00000370698.7	TSL:1	c.507+3_507+4delAAinsCC		splice_region intron	N/A	ENSP00000359732.3

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 as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Christianson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

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

Other links and lift over

dbSNP: rs730882187; hg19: chrX-135080347;