X-101657159-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_177949.4(ARMCX2):​c.430G>A​(p.Gly144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,073,677 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

ARMCX2
NM_177949.4 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.769
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06587666).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARMCX2NM_177949.4 linkc.430G>A p.Gly144Arg missense_variant Exon 6 of 6 ENST00000356824.9 NP_808818.1 Q7L311A0A024RCG7A8K5M7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARMCX2ENST00000356824.9 linkc.430G>A p.Gly144Arg missense_variant Exon 6 of 6 1 NM_177949.4 ENSP00000349281.4 Q7L311

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
0.00000279
AC:
3
AN:
1073677
Hom.:
0
Cov.:
33
AF XY:
0.00000288
AC XY:
1
AN XY:
347363
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000195
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000241
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 01, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.430G>A (p.G144R) alteration is located in exon 6 (coding exon 1) of the ARMCX2 gene. This alteration results from a G to A substitution at nucleotide position 430, causing the glycine (G) at amino acid position 144 to be replaced by an arginine (R). 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
0.069
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.0040
DANN
Benign
0.53
DEOGEN2
Benign
0.015
T;T;T;T;T
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.42
.;.;T;T;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.066
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L;L;L;.;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.4
N;N;N;N;N
REVEL
Benign
0.018
Sift
Benign
0.18
T;T;T;T;T
Sift4G
Benign
0.11
T;T;T;.;.
Polyphen
0.0010
B;B;B;.;.
Vest4
0.047
MutPred
0.36
Loss of catalytic residue at V145 (P = 0.0396);Loss of catalytic residue at V145 (P = 0.0396);Loss of catalytic residue at V145 (P = 0.0396);Loss of catalytic residue at V145 (P = 0.0396);Loss of catalytic residue at V145 (P = 0.0396);
MVP
0.082
MPC
0.44
ClinPred
0.042
T
GERP RS
-9.6
Varity_R
0.071
gMVP
0.079

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.

Other links and lift over

dbSNP: rs149321969; hg19: chrX-100912145; API