rs782106250

Variant names:

• chrX-135998100-T-C
• rs782106250
• NM_001379110.1:c.370-8T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001379110.1(SLC9A6):​c.370-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000072 in 833,367 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000072 (0 hom. 4 hem.)
• Consequence: SLC9A6 NM_001379110.1 splice_region, intron
• Scores: Splicing: ADA: 0.0003401
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.89
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant X-135998100-T-C is Benign according to our data. Variant chrX-135998100-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 436773.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000072 (6/833367) while in subpopulation SAS AF = 0.000124 (6/48474). AF 95% confidence interval is 0.0000533. There are 0 homozygotes in GnomAdExome4. There are 4 alleles in the male GnomAdExome4 subpopulation. Median coverage is 15. This position passed quality control check.
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.370-8T>C		splice_region_variant, intron_variant	Intron 3 of 17	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.370-8T>C		splice_region_variant, intron_variant	Intron 3 of 17	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.526-8T>C		splice_region_variant, intron_variant	Intron 2 of 15	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.430-8T>C		splice_region_variant, intron_variant	Intron 2 of 15	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.370-8T>C		splice_region_variant, intron_variant	Intron 3 of 16	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000221 AC: 4 AN: 181181 AF XY: 0.0000302

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: 0.00000720 AC: 6 AN: 833367 Hom.: 0 Cov.: 15 AF XY: 0.0000167 AC XY: 4 AN XY: 238937

African (AFR) AF: 0.00 AC: 0 AN: 21449

American (AMR) AF: 0.00 AC: 0 AN: 34816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17729

East Asian (EAS) AF: 0.00 AC: 0 AN: 28934

South Asian (SAS) AF: 0.000124 AC: 6 AN: 48474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3318

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 601185

Other (OTH) AF: 0.00 AC: 0 AN: 37092

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 12, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00034
dbscSNV1_RF	Benign	0.028
SpliceAI score (max)		0.0		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: rs782106250; hg19: chrX-135080259;