chrX-135985504-T-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1
The ENST00000370695.8(SLC9A6):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000814 in 982,839 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000081 ( 0 hom. 4 hem. )
Consequence
SLC9A6
ENST00000370695.8 start_lost
ENST00000370695.8 start_lost
Scores
5
2
6
Clinical Significance
Conservation
PhyloP100: 1.01
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 Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC9A6 | NM_001379110.1 | c.-57+27T>A | intron_variant | ENST00000630721.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC9A6 | ENST00000630721.3 | c.-57+27T>A | intron_variant | 4 | NM_001379110.1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome AF: 0.00000814 AC: 8AN: 982839Hom.: 0 Cov.: 29 AF XY: 0.0000130 AC XY: 4AN XY: 308177
GnomAD4 exome
AF:
AC:
8
AN:
982839
Hom.:
Cov.:
29
AF XY:
AC XY:
4
AN XY:
308177
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 22
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 submitter | clinical testing | GeneDx | Apr 28, 2022 | Not observed in large population cohorts (gnomAD); Initiation codon variant in a region of a gene for which loss of function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
B;B
Vest4
MutPred
Gain of ubiquitination at M1 (P = 0.0428);Gain of ubiquitination at M1 (P = 0.0428);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at