NM_001379110.1:c.447+3_447+4delAAinsCC

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 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. 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

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-135998188-AA-CC is Pathogenic according to our data. Variant chrX-135998188-AA-CC is described in ClinVar as [Pathogenic]. Clinvar id is 11478.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.447+3_447+4delAAinsCC		splice_region_variant, intron_variant	Intron 4 of 17	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.447+3_447+4delAAinsCC		splice_region_variant, intron_variant	Intron 4 of 17	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.603+3_603+4delAAinsCC		splice_region_variant, intron_variant	Intron 3 of 15	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.507+3_507+4delAAinsCC		splice_region_variant, intron_variant	Intron 3 of 15	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.447+3_447+4delAAinsCC		splice_region_variant, intron_variant	Intron 4 of 16	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

Apr 01, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs730882187; hg19: chrX-135080347;