rs144316388

Variant names:

• chrX-135998508-T-C
• rs144316388
• NM_001379110.1:c.474T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001379110.1(SLC9A6):​c.474T>C​(p.Ser158Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,176,895 control chromosomes in the GnomAD database, including 17 homozygotes. There are 311 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (6 hom., 153 hem., cov: 22)
  • Exomes 𝑓: 0.00060 (11 hom. 158 hem.)
• Consequence: SLC9A6 NM_001379110.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.208
• Publications: 1 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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-135998508-T-C is Benign according to our data. Variant chrX-135998508-T-C is described in ClinVar as Benign. ClinVar VariationId is 139200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.208 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00616 (681/110496) while in subpopulation AFR AF = 0.0214 (651/30408). AF 95% confidence interval is 0.02. There are 6 homozygotes in GnomAd4. There are 153 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 XL gene

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.474T>C	p.Ser158Ser	synonymous	Exon 5 of 18	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.630T>C	p.Ser210Ser	synonymous	Exon 4 of 17	NP_001425671.1
	SLC9A6	NM_001042537.2		c.630T>C	p.Ser210Ser	synonymous	Exon 4 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.474T>C	p.Ser158Ser	synonymous	Exon 5 of 18	ENSP00000487486.2	A0A0D9SGH0
	SLC9A6	ENST00000370695.8	TSL:1	c.630T>C	p.Ser210Ser	synonymous	Exon 4 of 16	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.534T>C	p.Ser178Ser	synonymous	Exon 4 of 16	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes AF: 0.00617 AC: 681 AN: 110451 Hom.: 6 Cov.: 22

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00252

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: 0.00270

GnomAD2 exomes AF: 0.00193 AC: 316 AN: 163836 AF XY: 0.000933

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000603 AC: 643 AN: 1066399 Hom.: 11 Cov.: 29 AF XY: 0.000460 AC XY: 158 AN XY: 343139

African (AFR) AF: 0.0216 AC: 541 AN: 24998

American (AMR) AF: 0.000925 AC: 28 AN: 30279

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18534

East Asian (EAS) AF: 0.00 AC: 0 AN: 29465

South Asian (SAS) AF: 0.0000429 AC: 2 AN: 46571

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39766

Middle Eastern (MID) AF: 0.000749 AC: 3 AN: 4005

European-Non Finnish (NFE) AF: 0.00000966 AC: 8 AN: 828091

Other (OTH) AF: 0.00136 AC: 61 AN: 44690

GnomAD4 genome AF: 0.00616 AC: 681 AN: 110496 Hom.: 6 Cov.: 22 AF XY: 0.00467 AC XY: 153 AN XY: 32770

African (AFR) AF: 0.0214 AC: 651 AN: 30408

American (AMR) AF: 0.00251 AC: 26 AN: 10347

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3574

South Asian (SAS) AF: 0.00 AC: 0 AN: 2609

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52775

Other (OTH) AF: 0.00267 AC: 4 AN: 1499

Alfa AF: 0.0113 Hom.: 107

Bravo AF: 0.00788

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Christianson syndrome (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	SLC9A6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.7
DANN	Benign	0.43
PhyloP100		-0.21
Mutation Taster		=99/1	polymorphism (auto)

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: rs144316388; hg19: chrX-135080667;