X-135985154-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

ACMG classification

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 GnomAd at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A6	NM_001400909.1	c.-35-470C>T		intron_variant
SLC9A6	NM_001400910.1	c.-56-449C>T		intron_variant
SLC9A6	NM_001400911.1	c.-56-449C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 1644 AN: 111454 Hom.: 16 Cov.: 22 AF XY: 0.0130 AC XY: 437 AN XY: 33630

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.: 17 Cov.: 0 AF XY: 0.0211 AC XY: 336 AN XY: 15888

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.: 16 Cov.: 22 AF XY: 0.0129 AC XY: 436 AN XY: 33679

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

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	13
Dann	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138591582; hg19: chrX-135067313;