Variant ENST00000370701:c.-399G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000370701(SLC9A6):c.-399G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 150,736 control chromosomes in the GnomAD database, including 25 homozygotes. There are 483 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 25 hom., 454 hem., cov: 22)

Exomes 𝑓: 0.0031 ( 0 hom. 29 hem. )

Consequence

SLC9A6
ENST00000370701 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37

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=-0.5).

BP6

Variant X-135985135-G-A is Benign according to our data. Variant chrX-135985135-G-A is described in ClinVar as [Benign]. Clinvar id is 672939.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
SLC9A6	NM_001400909.1 link	c.-35-489G>A	intron_variant	Intron 2 of 17	NP_001387838.1
SLC9A6	NM_001400910.1 link	c.-56-468G>A	intron_variant	Intron 1 of 16	NP_001387839.1
SLC9A6	NM_001400911.1 link	c.-56-468G>A	intron_variant	Intron 1 of 16	NP_001387840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000370701 link	c.-399G>A		5_prime_UTR_variant	Exon 1 of 17	1		ENSP00000359735.1		Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

1756

AN:

111202

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

451

AN XY:

33416

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000943

Gnomad OTH

AF:

0.00798

GnomAD4 exome

AF:

0.00314

AC:

124

AN:

39492

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

AN XY:

9264

show subpopulations

Gnomad4 AFR exome

AF:

0.0586

Gnomad4 AMR exome

AF:

0.00873

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00272

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000766

Gnomad4 OTH exome

AF:

0.00818

GnomAD4 genome

AF:

0.0158

AC:

1759

AN:

111244

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

454

AN XY:

33468

show subpopulations

Gnomad4 AFR

AF:

0.0539

Gnomad4 AMR

AF:

0.00891

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000943

Gnomad4 OTH

AF:

0.00788

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0185

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.50

CADD

Benign

DANN

Benign

0.88

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