X-135985525-G-A

Variant names:

• chrX-135985525-G-A
• ENST00000370695.8:c.23G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042537.2(SLC9A6):​c.23G>A​(p.Arg8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: SLC9A6 NM_001042537.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.246

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08752462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.-57+48G>A		intron_variant	Intron 1 of 17	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000370695.8	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000630721.3	c.-57+48G>A		intron_variant	Intron 1 of 17	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370701.6	c.-57+48G>A		intron_variant	Intron 1 of 16	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 25, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	.;T
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.75	T;T
M_CAP	Pathogenic	0.73	D
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.24	N;N
REVEL	Benign	0.035
Sift	Benign	0.27	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0050	B;B
Vest4		0.16
MutPred		0.20		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.068
MPC		1.2
ClinPred		0.038	T
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.045
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-135067684;