rs398124508

Variant names:

• chrX-25007238-AGGCGGCGGCGGC-A
• rs398124508
• NM_139058.3:c.1309_1320delGCCGCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chrX-25007238-AGGCGGCGGCGGC-A
• chrX-25007238-AGGCGGCGGCGGC-AGGC
• chrX-25007238-AGGCGGCGGCGGC-AGGCGGC
• chrX-25007238-AGGCGGCGGCGGC-AGGCGGCGGC
• chrX-25007238-AGGCGGCGGCGGC-AGGCGGCGGCGGCGGC
• chrX-25007238-AGGCGGCGGCGGC-AGGCGGCGGCGGCGGCGGC
• chrX-25007238-AGGCGGCGGCGGC-AGGCGGCGGCGGCGGCGGCGGC
• chrX-25007238-AGGCGGCGGCGGC-AGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_139058.3(ARX):​c.1309_1320delGCCGCCGCCGCC​(p.Ala437_Ala440del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 1,126,822 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 9.8e-7 (0 hom. 0 hem.)
• Consequence: ARX NM_139058.3 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_139058.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARX	NM_139058.3	c.1309_1320delGCCGCCGCCGCC	p.Ala437_Ala440del	conservative_inframe_deletion	Exon 4 of 5	ENST00000379044.5	NP_620689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARX	ENST00000379044.5	c.1309_1320delGCCGCCGCCGCC	p.Ala437_Ala440del	conservative_inframe_deletion	Exon 4 of 5	1	NM_139058.3	ENSP00000368332.4
ARX	ENST00000637993.1	c.-81_-70delGCCGCCGCCGCC		upstream_gene_variant		5		ENSP00000490122.1

Frequencies

GnomAD3 genomes AF: 0.00000901 AC: 1 AN: 111037 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33353

Gnomad AFR AF: 0.0000328

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.84e-7 AC: 1 AN: 1015785 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 324265

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: 0.0000223

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000901 AC: 1 AN: 111037 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33353

Gnomad4 AFR AF: 0.0000328

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs398124508; hg19: chrX-25025355;