chrX-101657276-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_177949.4(ARMCX2):​c.313G>C​(p.Ala105Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,455 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A105T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Consequence

ARMCX2
NM_177949.4 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0640
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06735948).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARMCX2NM_177949.4 linkc.313G>C p.Ala105Pro 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.313G>C p.Ala105Pro missense_variant Exon 6 of 6 1 NM_177949.4 ENSP00000349281.4 Q7L311

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
3
AN:
113214
Hom.:
0
Cov.:
24
AF XY:
0.0000283
AC XY:
1
AN XY:
35352
show subpopulations
Gnomad AFR
AF:
0.0000962
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
GnomAD4 exome
AF:
0.00000183
AC:
2
AN:
1095241
Hom.:
0
Cov.:
34
AF XY:
0.00000554
AC XY:
2
AN XY:
361091
show subpopulations
Gnomad4 AFR exome
AF:
0.0000380
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
AF:
0.0000265
AC:
3
AN:
113214
Hom.:
0
Cov.:
24
AF XY:
0.0000283
AC XY:
1
AN XY:
35352
show subpopulations
Gnomad4 AFR
AF:
0.0000962
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:
0.0000264
ESP6500AA
AF:
0.000261
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.313G>C (p.A105P) alteration is located in exon 6 (coding exon 1) of the ARMCX2 gene. This alteration results from a G to C substitution at nucleotide position 313, causing the alanine (A) at amino acid position 105 to be replaced by a proline (P). 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
0.086
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
6.5
DANN
Benign
0.90
DEOGEN2
Benign
0.023
T;T;T;T;T
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.46
.;.;T;T;T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.067
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N;N;N;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.75
N;N;N;N;N
REVEL
Benign
0.013
Sift
Benign
0.11
T;T;T;T;T
Sift4G
Benign
0.13
T;T;T;.;.
Polyphen
0.0010
B;B;B;.;.
Vest4
0.078
MVP
0.34
MPC
0.49
ClinPred
0.025
T
GERP RS
-0.14
Varity_R
0.11
gMVP
0.12

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: rs369060938; hg19: chrX-100912262; API