rs1060502675

Variant names:

• chrX-135994822-A-G
• rs1060502675
• NM_001379110.1:c.206A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001379110.1(SLC9A6):​c.206A>G​(p.His69Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,073 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Likely benign (★). The gene SLC9A6 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SLC9A6 NM_001379110.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.65
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-135994822-A-G is Benign according to our data. Variant chrX-135994822-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 409978.Status of the report is criteria_provided_single_submitter, 1 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.206A>G	p.His69Arg	missense	Exon 3 of 18	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.362A>G	p.His121Arg	missense	Exon 2 of 17	NP_001425671.1
	SLC9A6	NM_001042537.2		c.362A>G	p.His121Arg	missense	Exon 2 of 16	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.206A>G	p.His69Arg	missense	Exon 3 of 18	ENSP00000487486.2	A0A0D9SGH0
	SLC9A6	ENST00000370695.8	TSL:1	c.362A>G	p.His121Arg	missense	Exon 2 of 16	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.362A>G	p.His121Arg	missense	Exon 2 of 16	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098073 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363437

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40531

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841985

Other (OTH) AF: 0.00 AC: 0 AN: 46092

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Christianson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Benign	0.84
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		4.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.27
Sift	Benign	0.68	T
Sift4G	Benign	0.61	T
Polyphen		0.0040	B
Vest4		0.43
MutPred		0.58		Gain of solvent accessibility (P = 0.0171)
MVP		0.93
MPC		1.7
ClinPred		0.53	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.51
gMVP		0.89
Mutation Taster		=40/60	disease causing

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: rs1060502675; hg19: chrX-135076981; COSMIC: COSV65789175;