Genetic Variant ARMCX2:p.Gly144Arg (chrX-101657159-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_177949.4(ARMCX2):c.430G>C(p.Gly144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000931 in 1,073,678 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

ARMCX2
NM_177949.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.769

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06562102).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177949.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMCX2	NM_177949.4	MANE Select	c.430G>C	p.Gly144Arg	missense	Exon 6 of 6	NP_808818.1	Q7L311
ARMCX2	NM_001282231.2		c.430G>C	p.Gly144Arg	missense	Exon 6 of 6	NP_001269160.1	Q7L311
ARMCX2	NM_014782.7		c.430G>C	p.Gly144Arg	missense	Exon 5 of 5	NP_055597.1	Q7L311

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMCX2	ENST00000356824.9	TSL:1 MANE Select	c.430G>C	p.Gly144Arg	missense	Exon 6 of 6	ENSP00000349281.4	Q7L311
ARMCX2	ENST00000328766.9	TSL:1	c.430G>C	p.Gly144Arg	missense	Exon 5 of 5	ENSP00000331662.5	Q7L311
ARMCX2	ENST00000330154.6	TSL:1	c.430G>C	p.Gly144Arg	missense	Exon 3 of 3	ENSP00000328631.2	Q7L311

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.31e-7

AC:

AN:

1073678

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25433

American (AMR)

AF:

0.00

AC:

AN:

31303

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17864

East Asian (EAS)

AF:

0.00

AC:

AN:

29861

South Asian (SAS)

AF:

0.00

AC:

AN:

51223

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4001

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

829455

Other (OTH)

AF:

0.00

AC:

AN:

44770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0030

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.015

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.42

M_CAP

Benign

0.0031

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

-0.77

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

REVEL

Benign

0.018

Sift

Benign

0.18

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.047

MutPred

0.36

Loss of catalytic residue at V145 (P = 0.0396)

MVP

0.082

MPC

0.44

ClinPred

0.041

GERP RS

-9.6

Varity_R

0.071

gMVP

0.079

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over