Variant X-101625086-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000471229.7(ARMCX3):c.107A>C(p.Glu36Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000319 in 1,190,460 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000033 ( 0 hom. 18 hem. )

Consequence

ARMCX3
ENST00000471229.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

ARMCX3 (HGNC:24065): (armadillo repeat containing X-linked 3) This gene encodes a member of the ALEX family of proteins which may play a role in tumor suppression. The encoded protein contains a potential N-terminal transmembrane domain and a single Armadillo (arm) repeat. Other proteins containing the arm repeat are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is closely localized with other family members on the X chromosome. Three transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ARMCX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21485618).

BS2

High Hemizygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX3	NM_177947.3 linkuse as main transcript	c.107A>C	p.Glu36Ala	missense_variant	5/5	ENST00000471229.7	NP_808816.1	Q9UH62A0A024RCF9
ARMCX3	NM_016607.4 linkuse as main transcript	c.107A>C	p.Glu36Ala	missense_variant	5/5		NP_057691.1	Q9UH62A0A024RCF9
ARMCX3	NM_177948.3 linkuse as main transcript	c.107A>C	p.Glu36Ala	missense_variant	5/5		NP_808817.1	Q9UH62A0A024RCF9
ARMCX3	XM_005262141.4 linkuse as main transcript	c.107A>C	p.Glu36Ala	missense_variant	5/5		XP_005262198.1	Q9UH62A0A024RCF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMCX3	ENST00000471229.7 linkuse as main transcript	c.107A>C	p.Glu36Ala	missense_variant	5/5	1	NM_177947.3	ENSP00000454483.1		Q9UH62

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112413

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34553

show subpopulations

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:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000334

AC:

AN:

1078047

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

349209

show subpopulations

Gnomad4 AFR exome

AF:

0.0000389

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000199

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000372

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112413

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34553

show subpopulations

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:

0.0000375

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.107A>C (p.E36A) alteration is located in exon 5 (coding exon 1) of the ARMCX3 gene. This alteration results from a A to C substitution at nucleotide position 107, causing the glutamic acid (E) at amino acid position 36 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

T;T;T;.;T

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.74

.;.;T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.21

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;.;.;N

MutationTaster

Benign

0.85

N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.33

N;N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.042

D;D;D;D;D

Sift4G

Uncertain

0.040

D;D;D;D;D

Polyphen

0.25

B;B;.;.;B

Vest4

0.24

MutPred

0.25

Loss of ubiquitination at K37 (P = 0.0313);Loss of ubiquitination at K37 (P = 0.0313);Loss of ubiquitination at K37 (P = 0.0313);Loss of ubiquitination at K37 (P = 0.0313);Loss of ubiquitination at K37 (P = 0.0313);

MVP

0.95

MPC

2.0

ClinPred

0.66

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over