rs1313243538

chrX-25013644-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_139058.3(ARX):c.351C>A(p.Ala117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 761,271 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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 0.000019 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000031 (0 hom. 8 hem.)
• Consequence: ARX NM_139058.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.789

Genes affected

ARX (HGNC:18060): (aristaless related homeobox) This gene is a homeobox-containing gene expressed during development. The expressed protein contains two conserved domains, a C-peptide (or aristaless domain) and the prd-like class homeobox domain. It is a member of the group-II aristaless-related protein family whose members are expressed primarily in the central and/or peripheral nervous system. This gene is thought to be involved in CNS development. Expansion of a polyalanine tract and other mutations in this gene cause X-linked cognitive disability and epilepsy. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-25013644-G-T is Benign according to our data. Variant chrX-25013644-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 540223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.789 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARX	NM_139058.3	c.351C>A	p.Ala117=	synonymous_variant	2/5	ENST00000379044.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARX	ENST00000379044.5	c.351C>A	p.Ala117=	synonymous_variant	2/5	1	NM_139058.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000188 AC: 2 AN: 106647 Hom.: 0 Cov.: 22 AF XY: 0.0000316 AC XY: 1 AN XY: 31639

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000393

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000306 AC: 20 AN: 654624 Hom.: 0 Cov.: 31 AF XY: 0.0000402 AC XY: 8 AN XY: 198926

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000335

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000188 AC: 2 AN: 106647 Hom.: 0 Cov.: 22 AF XY: 0.0000316 AC XY: 1 AN XY: 31651

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000393

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked, with or without seizures, arx-related;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	10
Dann	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs1313243538; hg19: chrX-25031761;