chrX-135985527-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000370695.8(SLC9A6):​c.25G>A​(p.Ala9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000981 in 1,019,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9S) has been classified as Benign.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.8e-7 ( 0 hom. 1 hem. )

Consequence

SLC9A6
ENST00000370695.8 missense

Scores

2
1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

0 publications found
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]
SLC9A6 Gene-Disease associations (from GenCC):
  • Christianson syndrome
    Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1658698).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC9A6NM_001379110.1 linkc.-57+50G>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
SLC9A6ENST00000370695.8 linkc.25G>A p.Ala9Thr missense_variant Exon 1 of 16 1 ENSP00000359729.4 Q92581-2
SLC9A6ENST00000370698.7 linkc.25G>A p.Ala9Thr missense_variant Exon 1 of 16 1 ENSP00000359732.3 Q92581-1
SLC9A6ENST00000630721.3 linkc.-57+50G>A intron_variant Intron 1 of 17 4 NM_001379110.1 ENSP00000487486.2 A0A0D9SGH0
SLC9A6ENST00000370701.6 linkc.-57+50G>A intron_variant Intron 1 of 16 1 ENSP00000359735.1 Q92581-3

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
9.81e-7
AC:
1
AN:
1019734
Hom.:
0
Cov.:
30
AF XY:
0.00000312
AC XY:
1
AN XY:
320410
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
23701
American (AMR)
AF:
0.00
AC:
0
AN:
25522
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15932
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27393
South Asian (SAS)
AF:
0.00
AC:
0
AN:
45254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
28882
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3004
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
807135
Other (OTH)
AF:
0.0000233
AC:
1
AN:
42911
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.098
.;T
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.73
T;T
M_CAP
Pathogenic
0.66
D
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L
PhyloP100
2.1
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.36
N;N
REVEL
Benign
0.030
Sift
Benign
0.12
T;T
Sift4G
Benign
0.54
T;T
Polyphen
0.0050
B;B
Vest4
0.27
MutPred
0.24
Gain of phosphorylation at A9 (P = 0.0068);Gain of phosphorylation at A9 (P = 0.0068);
MVP
0.22
MPC
1.0
ClinPred
0.057
T
GERP RS
2.9
PromoterAI
0.085
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.064
gMVP
0.29
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

Publications

Other links and lift over

dbSNP: rs201523857; hg19: chrX-135067686; API