chrX-135985516-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000370695.8(SLC9A6):​c.14G>C​(p.Gly5Ala) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G5C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Consequence

SLC9A6
ENST00000370695.8 missense

Scores

3
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.1415165).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC9A6NM_001379110.1 linkuse as main transcriptc.-57+39G>C intron_variant ENST00000630721.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC9A6ENST00000630721.3 linkuse as main transcriptc.-57+39G>C intron_variant 4 NM_001379110.1

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
LINK: link

Submissions by phenotype

Christianson syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJun 10, 2023This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 5 of the SLC9A6 protein (p.Gly5Ala). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SLC9A6-related conditions. This variant is not present in population databases (gnomAD no frequency). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
.;T
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.73
T;T
M_CAP
Pathogenic
0.65
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.14
N;N
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.39
N;N
REVEL
Benign
0.13
Sift
Benign
0.16
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0
B;B
Vest4
0.18
MutPred
0.36
Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP
0.13
MPC
1.1
ClinPred
0.092
T
GERP RS
4.0
Varity_R
0.13
gMVP
0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2089318307; hg19: chrX-135067675; API