Variant X-135985154-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect
SLC9A6	NM_001400909.1 linkuse as main transcript	c.-35-470C>T	intron_variant
SLC9A6	NM_001400910.1 linkuse as main transcript	c.-56-449C>T	intron_variant
SLC9A6	NM_001400911.1 linkuse as main transcript	c.-56-449C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Appris	UniProt
SLC9A6	ENST00000370701.6 linkuse as main transcript	c.-380C>T	5_prime_UTR_variant	1/17	1	A1	Q92581-3
SLC9A6	ENST00000636092.1 linkuse as main transcript	c.-56-449C>T	intron_variant		5	A1	Q92581-3
SLC9A6	ENST00000636347.1 linkuse as main transcript	c.-35-470C>T	intron_variant		5	A1	Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

1644

AN:

111454

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

437

AN XY:

33630

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

Gnomad4 AFR exome

AF:

0.00483

Gnomad4 AMR exome

AF:

0.00748

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0248

Gnomad4 OTH exome

AF:

0.0175

GnomAD4 genome

AF:

0.0147

AC:

1643

AN:

111493

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

436

AN XY:

33679

show subpopulations

Gnomad4 AFR

AF:

0.00328

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00706

Gnomad4 FIN

AF:

0.00666

Gnomad4 NFE

AF:

0.0237

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0188

Hom.:

102

Bravo

AF:

0.0142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.90

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over