rs17001258

Variant names:

• chrX-136010436-C-T
• rs17001258
• NM_001379110.1:c.744-6C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001438742.1(SLC9A6):​c.900-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,208,872 control chromosomes in the GnomAD database, including 69 homozygotes. There are 973 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (33 hom., 489 hem., cov: 23)
  • Exomes 𝑓: 0.0018 (36 hom. 484 hem.)
• Consequence: SLC9A6 NM_001438742.1 splice_region, intron
• Scores: Splicing: ADA: 0.0002719
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.32
• Publications: 2 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant X-136010436-C-T is Benign according to our data. Variant chrX-136010436-C-T is described in ClinVar as Benign. ClinVar VariationId is 139201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

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.744-6C>T		splice_region intron	N/A	NP_001366039.1
	SLC9A6	NM_001438742.1		c.900-6C>T		splice_region intron	N/A	NP_001425671.1
	SLC9A6	NM_001042537.2		c.900-6C>T		splice_region intron	N/A	NP_001036002.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.744-6C>T		splice_region intron	N/A	ENSP00000487486.2
	SLC9A6	ENST00000370695.8	TSL:1	c.900-6C>T		splice_region intron	N/A	ENSP00000359729.4
	SLC9A6	ENST00000370698.7	TSL:1	c.804-6C>T		splice_region intron	N/A	ENSP00000359732.3

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 1913 AN: 111818 Hom.: 33 Cov.: 23

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00932

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00864

GnomAD2 exomes AF: 0.00498 AC: 913 AN: 183393 AF XY: 0.00329

Gnomad AFR exome AF: 0.0625

Gnomad AMR exome AF: 0.00273

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000610

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00181 AC: 1990 AN: 1097005 Hom.: 36 Cov.: 29 AF XY: 0.00134 AC XY: 484 AN XY: 362397

African (AFR) AF: 0.0616 AC: 1625 AN: 26371

American (AMR) AF: 0.00378 AC: 133 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30191

South Asian (SAS) AF: 0.0000924 AC: 5 AN: 54110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40472

Middle Eastern (MID) AF: 0.00121 AC: 5 AN: 4134

European-Non Finnish (NFE) AF: 0.0000416 AC: 35 AN: 841101

Other (OTH) AF: 0.00406 AC: 187 AN: 46044

GnomAD4 genome AF: 0.0171 AC: 1916 AN: 111867 Hom.: 33 Cov.: 23 AF XY: 0.0144 AC XY: 489 AN XY: 34059

African (AFR) AF: 0.0585 AC: 1798 AN: 30721

American (AMR) AF: 0.00940 AC: 99 AN: 10532

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3586

South Asian (SAS) AF: 0.00 AC: 0 AN: 2687

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6006

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

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53257

Other (OTH) AF: 0.00854 AC: 13 AN: 1523

Alfa AF: 0.00827 Hom.: 242

Bravo AF: 0.0199

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Christianson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.6
DANN	Benign	0.83
PhyloP100		1.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.010
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: rs17001258; hg19: chrX-135092595;