Genetic Variant ENST00000370701.6:c.-380C>T (chrX-135985154-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000370701.6(SLC9A6):c.-380C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 175,759 control chromosomes in the GnomAD database, including 33 homozygotes. There are 772 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.015 ( 16 hom., 436 hem., cov: 22)

Exomes 𝑓: 0.020 ( 17 hom. 336 hem. )

Consequence

SLC9A6
ENST00000370701.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00

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

SLC9A6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-135985154-C-T is Benign according to our data. Variant chrX-135985154-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 669883.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0147 (1643/111493) while in subpopulation NFE AF = 0.0237 (1258/52996). AF 95% confidence interval is 0.0226. There are 16 homozygotes in GnomAd4. There are 436 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370701.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC9A6	NM_001400909.1	c.-35-470C>T	intron	N/A	NP_001387838.1	Q92581-3
SLC9A6	NM_001400910.1	c.-56-449C>T	intron	N/A	NP_001387839.1	Q92581-3
SLC9A6	NM_001400911.1	c.-56-449C>T	intron	N/A	NP_001387840.1	Q92581-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC9A6	ENST00000370701.6	TSL:1	c.-380C>T	5_prime_UTR	Exon 1 of 17	ENSP00000359735.1	Q92581-3
SLC9A6	ENST00000636092.1	TSL:5	c.-56-449C>T	intron	N/A	ENSP00000490406.1	Q92581-3
SLC9A6	ENST00000636347.1	TSL:5	c.-35-470C>T	intron	N/A	ENSP00000490648.1	Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

1644

AN:

111454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00332

Gnomad AMI

AF:

0.00147

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.00666

Gnomad MID

AF:

0.0293

Gnomad NFE

AF:

0.0237

Gnomad OTH

AF:

0.0120

GnomAD4 exome

AF:

0.0197

AC:

1264

AN:

64266

Hom.:

Cov.:

AF XY:

0.0211

AC XY:

336

AN XY:

15888

show subpopulations

African (AFR)

AF:

0.00483

AC:

AN:

2277

American (AMR)

AF:

0.00748

AC:

AN:

1872

Ashkenazi Jewish (ASJ)

AF:

0.0226

AC:

AN:

2256

East Asian (EAS)

AF:

0.00

AC:

AN:

4982

South Asian (SAS)

AF:

0.0104

AC:

AN:

671

European-Finnish (FIN)

AF:

0.0104

AC:

AN:

5278

Middle Eastern (MID)

AF:

0.0169

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.0248

AC:

1039

AN:

41947

Other (OTH)

AF:

0.0175

AC:

AN:

4687

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0147

AC:

1643

AN:

111493

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

436

AN XY:

33679

show subpopulations

African (AFR)

AF:

0.00328

AC:

101

AN:

30762

American (AMR)

AF:

0.0127

AC:

134

AN:

10576

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3546

South Asian (SAS)

AF:

0.00706

AC:

AN:

2691

European-Finnish (FIN)

AF:

0.00666

AC:

AN:

5858

Middle Eastern (MID)

AF:

0.0276

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0237

AC:

1258

AN:

52996

Other (OTH)

AF:

0.0118

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0188

Hom.:

102

Bravo

AF:

0.0142

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.0

PromoterAI

-0.010

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over