rs1060504684

Variant names:

• chrX-136016637-C-T
• rs1060504684
• NM_001379110.1:c.1081-8C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-136016637-C-T
• chrX-136016637-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_001379110.1(SLC9A6):​c.1081-8C>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 0.00000894 in 111,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 (★★). The gene SLC9A6 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000068 (0 hom. 4 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC9A6 NM_001379110.1 splice_region, intron
• Scores: Splicing: ADA: 0.00002500
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.238
• 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

Specifications for SLC9A6 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-136016637-C-T is Benign according to our data. Variant chrX-136016637-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 415899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	NM_001379110.1	MANE Select	c.1081-8C>T		splice_region intron	N/A	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.1237-8C>T		splice_region intron	N/A	NP_001425671.1
	SLC9A6	NM_001042537.2		c.1237-8C>T		splice_region intron	N/A	NP_001036002.1	Q92581-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.1081-8C>T		splice_region intron	N/A	ENSP00000487486.2	A0A0D9SGH0
	SLC9A6	ENST00000370695.8	TSL:1	c.1237-8C>T		splice_region intron	N/A	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.1141-8C>T		splice_region intron	N/A	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111898 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000951

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000549 AC: 1 AN: 182155 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000367

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000682 AC: 6 AN: 879975 Hom.: 0 Cov.: 17 AF XY: 0.0000156 AC XY: 4 AN XY: 255915

African (AFR) AF: 0.0000448 AC: 1 AN: 22302

American (AMR) AF: 0.0000287 AC: 1 AN: 34888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18001

East Asian (EAS) AF: 0.00 AC: 0 AN: 29191

South Asian (SAS) AF: 0.0000403 AC: 2 AN: 49639

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40365

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3686

European-Non Finnish (NFE) AF: 0.00000311 AC: 2 AN: 643054

Other (OTH) AF: 0.00 AC: 0 AN: 38849

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111898 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34078

African (AFR) AF: 0.00 AC: 0 AN: 30800

American (AMR) AF: 0.0000951 AC: 1 AN: 10517

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2697

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53175

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		-0.24
Mutation Taster		=43/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0020
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: rs1060504684; hg19: chrX-135098796;