rs185533973

Variant names:

• chrX-136024493-A-G
• rs185533973
• NM_001379110.1:c.1460+10A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001379110.1(SLC9A6):​c.1460+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,187,672 control chromosomes in the GnomAD database, including 11 homozygotes. There are 192 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (1 hom., 10 hem., cov: 23)
  • Exomes 𝑓: 0.00055 (10 hom. 182 hem.)
• Consequence: SLC9A6 NM_001379110.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.576
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-136024493-A-G is Benign according to our data. Variant chrX-136024493-A-G is described in ClinVar as Benign. ClinVar VariationId is 139204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000259 (29/111910) while in subpopulation EAS AF = 0.00785 (28/3569). AF 95% confidence interval is 0.00558. There are 1 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 10 XL gene

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.1460+10A>G		intron	N/A	NP_001366039.1
	SLC9A6	NM_001438742.1		c.1616+10A>G		intron	N/A	NP_001425671.1
	SLC9A6	NM_001042537.2		c.1616+10A>G		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.1460+10A>G		intron	N/A	ENSP00000487486.2
	SLC9A6	ENST00000370695.8	TSL:1	c.1616+10A>G		intron	N/A	ENSP00000359729.4
	SLC9A6	ENST00000370698.7	TSL:1	c.1520+10A>G		intron	N/A	ENSP00000359732.3

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 28 AN: 111858 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00754

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000662

GnomAD2 exomes AF: 0.000279 AC: 51 AN: 182746 AF XY: 0.000253

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00368

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000552 AC: 594 AN: 1075762 Hom.: 10 Cov.: 27 AF XY: 0.000531 AC XY: 182 AN XY: 342482

African (AFR) AF: 0.00 AC: 0 AN: 26016

American (AMR) AF: 0.00 AC: 0 AN: 35063

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19222

East Asian (EAS) AF: 0.0195 AC: 586 AN: 30101

South Asian (SAS) AF: 0.00 AC: 0 AN: 53425

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40511

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4067

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 821989

Other (OTH) AF: 0.000176 AC: 8 AN: 45368

GnomAD4 genome AF: 0.000259 AC: 29 AN: 111910 Hom.: 1 Cov.: 23 AF XY: 0.000293 AC XY: 10 AN XY: 34074

African (AFR) AF: 0.00 AC: 0 AN: 30868

American (AMR) AF: 0.00 AC: 0 AN: 10487

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00785 AC: 28 AN: 3569

South Asian (SAS) AF: 0.00 AC: 0 AN: 2670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5985

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53249

Other (OTH) AF: 0.000654 AC: 1 AN: 1529

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.000147

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Christianson syndrome (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		0.58
PromoterAI		-0.0056	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs185533973; hg19: chrX-135106652;