chrX-135985504-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2

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

Scores

5
2
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01
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 4 ACMG points.

PVS1
Start lost variant, no new inframe start found.
BS2
High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC9A6NM_001379110.1 linkuse as main transcriptc.-57+27T>A intron_variant ENST00000630721.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC9A6ENST00000630721.3 linkuse as main transcriptc.-57+27T>A intron_variant 4 NM_001379110.1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.00000814
AC:
8
AN:
982839
Hom.:
0
Cov.:
29
AF XY:
0.0000130
AC XY:
4
AN XY:
308177
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:
0.0000101
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 testingGeneDxApr 28, 2022Not 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.15
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.095
.;T
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Pathogenic
0.98
D
MetaRNN
Pathogenic
0.97
D;D
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
0.94
D;D;D
PROVEAN
Benign
-0.16
N;N
REVEL
Benign
0.27
Sift
Uncertain
0.0070
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0050
B;B
Vest4
0.73
MutPred
0.84
Gain of ubiquitination at M1 (P = 0.0428);Gain of ubiquitination at M1 (P = 0.0428);
MVP
0.98
ClinPred
0.95
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.84
gMVP
0.87

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: rs1006154022; hg19: chrX-135067663; API