X-135985492-C-CG

Variant names:

• chrX-135985492-C-CG
• rs782431608
• ENST00000370695.8:c.-5dupG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001438742.1(SLC9A6):​c.-5dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000934 in 963,399 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000093 (0 hom. 4 hem.)
• Consequence: SLC9A6 NM_001438742.1 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.477
• 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, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438742.1. 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.-57+21dupG		intron	N/A	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.-5dupG		5_prime_UTR	Exon 1 of 17	NP_001425671.1
	SLC9A6	NM_001042537.2		c.-5dupG		5_prime_UTR	Exon 1 of 16	NP_001036002.1	Q92581-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	ENST00000370695.8	TSL:1	c.-5dupG		5_prime_UTR	Exon 1 of 16	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.-5dupG		5_prime_UTR	Exon 1 of 16	ENSP00000359732.3	Q92581-1
	SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.-57+21dupG		intron	N/A	ENSP00000487486.2	A0A0D9SGH0

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00 AC: 0 AN: 37084 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000934 AC: 9 AN: 963399 Hom.: 0 Cov.: 27 AF XY: 0.0000134 AC XY: 4 AN XY: 298337

African (AFR) AF: 0.00 AC: 0 AN: 21173

American (AMR) AF: 0.00 AC: 0 AN: 16963

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14002

East Asian (EAS) AF: 0.00 AC: 0 AN: 25056

South Asian (SAS) AF: 0.00 AC: 0 AN: 39905

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2553

European-Non Finnish (NFE) AF: 0.0000116 AC: 9 AN: 778669

Other (OTH) AF: 0.00 AC: 0 AN: 40746

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs782431608; hg19: chrX-135067651;