Variant X-25015704-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000379044.5(ARX):c.34G>C(p.Glu12Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E12K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

ARX
ENST00000379044.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.89

Variant links:

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]

ARX links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARX	NM_139058.3 linkuse as main transcript	c.34G>C	p.Glu12Gln	missense_variant	1/5	ENST00000379044.5	NP_620689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARX	ENST00000379044.5 linkuse as main transcript	c.34G>C	p.Glu12Gln	missense_variant	1/5	1	NM_139058.3	ENSP00000368332	P1
ARX	ENST00000636609.1 linkuse as main transcript	n.36-59G>C		intron_variant, non_coding_transcript_variant		5
ARX	ENST00000637394.1 linkuse as main transcript	n.68-59G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

163002

Hom.:

AF XY:

0.0000190

AC XY:

AN XY:

52674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000154

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000276

AC:

AN:

1088898

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

356230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000669

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.39

MetaSVM

Uncertain

0.60

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.42

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

0.99

Vest4

0.14

MutPred

0.036

Gain of relative solvent accessibility (P = 0.1571);

MVP

0.92

MPC

1.1

ClinPred

0.62

GERP RS

5.3

Varity_R

0.37

gMVP

0.25

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over