rs188072063

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001379110.1(SLC9A6):​c.1662-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,197,139 control chromosomes in the GnomAD database, including 45 homozygotes. There are 4,024 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). The gene SLC9A6 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.0070 ( 4 hom., 221 hem., cov: 24)
Exomes 𝑓: 0.011 ( 41 hom. 3803 hem. )

Consequence

SLC9A6
NM_001379110.1 splice_region, intron

Scores

2
Splicing: ADA: 0.00006198
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.23

Publications

2 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, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant X-136040072-G-A is Benign according to our data. Variant chrX-136040072-G-A is described in ClinVar as Benign. ClinVar VariationId is 139208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00702 (787/112106) while in subpopulation NFE AF = 0.0114 (606/53238). AF 95% confidence interval is 0.0106. There are 4 homozygotes in GnomAd4. There are 221 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379110.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SLC9A6
NM_001379110.1
MANE Select
c.1662-4G>A
splice_region intron
N/ANP_001366039.1A0A0D9SGH0
SLC9A6
NM_001438742.1
c.1818-4G>A
splice_region intron
N/ANP_001425671.1
SLC9A6
NM_001042537.2
c.1728-4G>A
splice_region intron
N/ANP_001036002.1Q92581-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SLC9A6
ENST00000630721.3
TSL:4 MANE Select
c.1662-4G>A
splice_region intron
N/AENSP00000487486.2A0A0D9SGH0
SLC9A6
ENST00000370695.8
TSL:1
c.1728-4G>A
splice_region intron
N/AENSP00000359729.4Q92581-2
SLC9A6
ENST00000370698.7
TSL:1
c.1632-4G>A
splice_region intron
N/AENSP00000359732.3Q92581-1

Frequencies

GnomAD3 genomes
AF:
0.00702
AC:
787
AN:
112050
Hom.:
4
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.00120
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00944
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00522
Gnomad FIN
AF:
0.00313
Gnomad MID
AF:
0.00418
Gnomad NFE
AF:
0.0114
Gnomad OTH
AF:
0.00665
GnomAD2 exomes
AF:
0.00631
AC:
1124
AN:
178130
AF XY:
0.00647
show subpopulations
Gnomad AFR exome
AF:
0.000703
Gnomad AMR exome
AF:
0.00265
Gnomad ASJ exome
AF:
0.000135
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00404
Gnomad NFE exome
AF:
0.0109
Gnomad OTH exome
AF:
0.00704
GnomAD4 exome
AF:
0.0110
AC:
11910
AN:
1085033
Hom.:
41
Cov.:
28
AF XY:
0.0108
AC XY:
3803
AN XY:
351625
show subpopulations
African (AFR)
AF:
0.00138
AC:
36
AN:
26175
American (AMR)
AF:
0.00365
AC:
128
AN:
35088
Ashkenazi Jewish (ASJ)
AF:
0.000156
AC:
3
AN:
19287
East Asian (EAS)
AF:
0.0000332
AC:
1
AN:
30124
South Asian (SAS)
AF:
0.00527
AC:
282
AN:
53484
European-Finnish (FIN)
AF:
0.00435
AC:
176
AN:
40433
Middle Eastern (MID)
AF:
0.00295
AC:
12
AN:
4070
European-Non Finnish (NFE)
AF:
0.0130
AC:
10835
AN:
830729
Other (OTH)
AF:
0.00957
AC:
437
AN:
45643
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
373
746
1119
1492
1865
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
410
820
1230
1640
2050
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00702
AC:
787
AN:
112106
Hom.:
4
Cov.:
24
AF XY:
0.00644
AC XY:
221
AN XY:
34300
show subpopulations
African (AFR)
AF:
0.00120
AC:
37
AN:
30878
American (AMR)
AF:
0.00943
AC:
100
AN:
10600
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2653
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3561
South Asian (SAS)
AF:
0.00523
AC:
14
AN:
2675
European-Finnish (FIN)
AF:
0.00313
AC:
19
AN:
6078
Middle Eastern (MID)
AF:
0.00459
AC:
1
AN:
218
European-Non Finnish (NFE)
AF:
0.0114
AC:
606
AN:
53238
Other (OTH)
AF:
0.00657
AC:
10
AN:
1523
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
30
60
91
121
151
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00988
Hom.:
128
Bravo
AF:
0.00712

ClinVar

ClinVar submissions
Significance:Benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
5
not specified (5)
-
-
3
Christianson syndrome (3)
-
-
3
not provided (3)
-
-
1
Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.027
DANN
Benign
0.61
PhyloP100
-1.2
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000062
dbscSNV1_RF
Benign
0.016
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: rs188072063; hg19: chrX-135122231; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.