rs17001258

Positions:

• chrX-136010436-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001379110.1(SLC9A6):​c.744-6C>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_001379110.1 splice_region, intron
• Scores: Splicing: ADA: 0.0002719
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.32

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 139201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136010436-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.744-6C>T		splice_region_variant, intron_variant		ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.744-6C>T		splice_region_variant, intron_variant		4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.900-6C>T		splice_region_variant, intron_variant		1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.804-6C>T		splice_region_variant, intron_variant		1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.744-6C>T		splice_region_variant, intron_variant		1		ENSP00000359735.1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 1913 AN: 111818 Hom.: 33 Cov.: 23 AF XY: 0.0143 AC XY: 486 AN XY: 34000

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

GnomAD3 exomes AF: 0.00498 AC: 913 AN: 183393 Hom.: 22 AF XY: 0.00329 AC XY: 223 AN XY: 67841

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 SAS exome AF: 0.0000524

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

Gnomad4 AFR exome AF: 0.0616

Gnomad4 AMR exome AF: 0.00378

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000924

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000416

Gnomad4 OTH exome AF: 0.00406

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

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.00940

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.00648 Hom.: 86

Bravo AF: 0.0199

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Christianson syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.6
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs17001258; hg19: chrX-135092595;