X-135998932-C-T

Variant names:

• chrX-135998932-C-T
• rs1556617009
• NM_001379110.1:c.601C>T
• SLC9A6 p.Leu201Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001379110.1(SLC9A6):​c.601C>T​(p.Leu201Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,203,508 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L201L) has been classified as Likely benign. The gene SLC9A6 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: SLC9A6 NM_001379110.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.98
• 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: PanelApp Australia, ClinGen, G2P, Orphanet

ACMG classification

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant X-135998932-C-T is Benign according to our data. Variant chrX-135998932-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2824552.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.601C>T	p.Leu201Leu	synonymous	Exon 6 of 18	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.757C>T	p.Leu253Leu	synonymous	Exon 5 of 17	NP_001425671.1
	SLC9A6	NM_001042537.2		c.757C>T	p.Leu253Leu	synonymous	Exon 5 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.601C>T	p.Leu201Leu	synonymous	Exon 6 of 18	ENSP00000487486.2	A0A0D9SGH0
	SLC9A6	ENST00000370695.8	TSL:1	c.757C>T	p.Leu253Leu	synonymous	Exon 5 of 16	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.661C>T	p.Leu221Leu	synonymous	Exon 5 of 16	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111636 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 9.16e-7 AC: 1 AN: 1091872 Hom.: 0 Cov.: 28 AF XY: 0.00000280 AC XY: 1 AN XY: 357516

African (AFR) AF: 0.0000381 AC: 1 AN: 26280

American (AMR) AF: 0.00 AC: 0 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19335

East Asian (EAS) AF: 0.00 AC: 0 AN: 30160

South Asian (SAS) AF: 0.00 AC: 0 AN: 53994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4121

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 836423

Other (OTH) AF: 0.00 AC: 0 AN: 45880

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111636 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33840

African (AFR) AF: 0.0000325 AC: 1 AN: 30763

American (AMR) AF: 0.00 AC: 0 AN: 10432

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3609

South Asian (SAS) AF: 0.00 AC: 0 AN: 2703

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5937

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53110

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.00 Hom.: 0

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
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		2.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1556617009;

hg19: chrX-135081091;