chrX-135985673-C-G

Variant names:

• chrX-135985673-C-G
• rs782296172
• NM_001379110.1:c.15C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1 BP4

This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Ile5Met variant in SLC9A6 is 0.013% in Ashkenazi Jewish sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). Computational analysis prediction tools suggest that the p.Ile5Met variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Ile5Met variant in SLC9A6 is classified as likely benign based on the ACMG/AMP criteria (BS1, BP4). LINK:https://erepo.genome.network/evrepo/ui/classification/CA10524605/MONDO:0010278/016

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000041 (0 hom. 21 hem.)
• Consequence: SLC9A6 NM_001379110.1 missense
• Clinical Significance: Likely benign reviewed by expert panel U:1 B:4
• Conservation: PhyloP100: -0.100
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BS1: For more information check the summary or visit ClinGen Evidence Repository.

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.15C>G	p.Ile5Met	missense	Exon 2 of 18	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.171C>G	p.Ile57Met	missense	Exon 1 of 17	NP_001425671.1
	SLC9A6	NM_001042537.2		c.171C>G	p.Ile57Met	missense	Exon 1 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.15C>G	p.Ile5Met	missense	Exon 2 of 18	ENSP00000487486.2	A0A0D9SGH0
	SLC9A6	ENST00000370695.8	TSL:1	c.171C>G	p.Ile57Met	missense	Exon 1 of 16	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.171C>G	p.Ile57Met	missense	Exon 1 of 16	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes AF: 0.0000715 AC: 8 AN: 111855 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

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: 0.000151

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000382 AC: 7 AN: 183243 AF XY: 0.0000591

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000733

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000410 AC: 45 AN: 1098201 Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 21 AN XY: 363567

African (AFR) AF: 0.00 AC: 0 AN: 26402

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000511 AC: 43 AN: 842115

Other (OTH) AF: 0.0000434 AC: 2 AN: 46093

GnomAD4 genome AF: 0.0000715 AC: 8 AN: 111855 Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1 AN XY: 34029

African (AFR) AF: 0.00 AC: 0 AN: 30814

American (AMR) AF: 0.00 AC: 0 AN: 10670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3518

South Asian (SAS) AF: 0.00 AC: 0 AN: 2692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6035

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000151 AC: 8 AN: 53047

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.0000680

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000273

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	3	Christianson syndrome (3)
-	1	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.10
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.070
Sift	Benign	0.17	T
Sift4G	Benign	0.29	T
Polyphen		0.92	P
Vest4		0.34
MutPred		0.27		Loss of loop (P = 0.0986)
MVP		0.29
MPC		1.1
ClinPred		0.038	T
GERP RS		0.32
PromoterAI		-0.025	Neutral
Varity_R		0.15
gMVP		0.91
Mutation Taster		=97/3	polymorphism

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: rs782296172; hg19: chrX-135067832;