chrX-135985515-G-A

Variant summary

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

The ENST00000370695.8(SLC9A6):​c.13G>A​(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000004 in 1,000,179 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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. G5A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000040 ( 0 hom. 0 hem. )

Consequence

SLC9A6
ENST00000370695.8 missense

Scores

3
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183
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=0.11313021).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC9A6NM_001379110.1 linkuse as main transcriptc.-57+38G>A intron_variant ENST00000630721.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC9A6ENST00000630721.3 linkuse as main transcriptc.-57+38G>A intron_variant 4 NM_001379110.1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.00000400
AC:
4
AN:
1000179
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
313415
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000501
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMay 12, 2022Not 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
0.13
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
12
DANN
Benign
0.96
DEOGEN2
Benign
0.12
.;T
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.64
T;T
M_CAP
Pathogenic
0.67
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.34
N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.30
N;N
REVEL
Benign
0.053
Sift
Uncertain
0.029
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.025
B;B
Vest4
0.16
MutPred
0.34
Gain of phosphorylation at G5 (P = 9e-04);Gain of phosphorylation at G5 (P = 9e-04);
MVP
0.16
MPC
1.0
ClinPred
0.095
T
GERP RS
-0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.087
gMVP
0.57

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: rs895044278; hg19: chrX-135067674; API