X-135985474-T-C

Position:

chrX-135985474-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1BP6_ModerateBS1BS2

The NM_001400912.1(SLC9A6):c.-57+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,012,646 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 12 hem., cov: 22)

Exomes 𝑓: 0.000023 ( 0 hom. 2 hem. )

Consequence

SLC9A6
NM_001400912.1 splice_donor, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.695

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 Likely_benign. Variant got -2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 7.8, offset of 5, new splice context is: gagGTaggg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant X-135985474-T-C is Benign according to our data. Variant chrX-135985474-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 378617.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000193 (21/108811) while in subpopulation AMR AF= 0.00182 (19/10422). AF 95% confidence interval is 0.00119. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.-60T>C		5_prime_UTR_variant	1/18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC9A6	ENST00000630721 link	c.-60T>C	5_prime_UTR_variant	1/18	4	NM_001379110.1	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695 link	c.-29T>C	5_prime_UTR_variant	1/16	1		ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698 link	c.-29T>C	5_prime_UTR_variant	1/16	1		ENSP00000359732.3	Q92581-1
SLC9A6	ENST00000370701 link	c.-60T>C	5_prime_UTR_variant	1/17	1		ENSP00000359735.1	Q92581-3

Frequencies

GnomAD3 genomes

AF:

0.000193

AC:

AN:

108767

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

AN XY:

31733

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00437

Gnomad NFE

AF:

0.0000192

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000407

AC:

AN:

14745

Hom.:

AF XY:

0.000705

AC XY:

AN XY:

1419

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000232

AC:

AN:

903835

Hom.:

Cov.:

AF XY:

0.00000745

AC XY:

AN XY:

268493

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000561

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:

0.0000175

Gnomad4 OTH exome

AF:

0.0000524

GnomAD4 genome

AF:

0.000193

AC:

AN:

108811

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

AN XY:

31785

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00182

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000192

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 19, 2015

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. -

SLC9A6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 29, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

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