X-135985135-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000370701.6(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 ENST00000370701.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.37

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=-0.5).
• 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	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A6	NM_001400909.1	c.-35-489G>A		intron_variant
SLC9A6	NM_001400910.1	c.-56-468G>A		intron_variant
SLC9A6	NM_001400911.1	c.-56-468G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A6	ENST00000370701.6	c.-399G>A		5_prime_UTR_variant	1/17	1		A1
SLC9A6	ENST00000636092.1	c.-56-468G>A		intron_variant		5		A1
SLC9A6	ENST00000636347.1	c.-35-489G>A		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 1756 AN: 111202 Hom.: 25 Cov.: 22 AF XY: 0.0135 AC XY: 451 AN XY: 33416

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.: 0 Cov.: 0 AF XY: 0.00313 AC XY: 29 AN XY: 9264

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.: 25 Cov.: 22 AF XY: 0.0136 AC XY: 454 AN XY: 33468

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.: 48

Bravo AF: 0.0185

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.50
Cadd	Benign	16
Dann	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs145928242; hg19: chrX-135067294;