Genetic Variant ARMCX2:p.Arg288Gly (chrX-101656727-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177949.4(ARMCX2):c.862A>G(p.Arg288Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 110,957 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 21)

Consequence

ARMCX2
NM_177949.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

Variant links:

Genes affected

ARMCX2 (HGNC:16869): (armadillo repeat containing X-linked 2) This gene encodes a protein containing a potential N-terminal transmembrane domain and multiple armadillo (arm) repeats. Proteins containing arm repeats are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is located in a cluster of related genes on chromosome X. There is a pseudogene for this gene on chromosome 7. Alternative splicing in the 5' UTR results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2013]

ARMCX2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0816299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX2	NM_177949.4 link	c.862A>G	p.Arg288Gly	missense_variant	Exon 6 of 6	ENST00000356824.9	NP_808818.1	Q7L311A0A024RCG7A8K5M7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARMCX2	ENST00000356824.9 link	c.862A>G	p.Arg288Gly	missense_variant	Exon 6 of 6	1	NM_177949.4	ENSP00000349281.4	Q7L311
ARMCX2	ENST00000328766.9 link	c.862A>G	p.Arg288Gly	missense_variant	Exon 5 of 5	1		ENSP00000331662.5	Q7L311
ARMCX2	ENST00000330154.6 link	c.862A>G	p.Arg288Gly	missense_variant	Exon 3 of 3	1		ENSP00000328631.2	Q7L311

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

110957

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33179

show subpopulations

Gnomad AFR

AF:

0.0000984

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

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183398

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67838

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

Cov.:

GnomAD4 genome

AF:

0.0000270

AC:

AN:

110957

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33179

show subpopulations

Gnomad4 AFR

AF:

0.0000984

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:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.862A>G (p.R288G) alteration is located in exon 6 (coding exon 1) of the ARMCX2 gene. This alteration results from a A to G substitution at nucleotide position 862, causing the arginine (R) at amino acid position 288 to be replaced by a glycine (G). 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

0.23

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

T;T;T

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.51

.;.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.082

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.59

T;T;T

Polyphen

0.28

B;B;B

Vest4

0.21

MVP

0.17

MPC

0.48

ClinPred

0.084

GERP RS

4.3

Varity_R

0.17

gMVP

0.37

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