chrX-101657276-C-T

Variant summary

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

The NM_177949.4(ARMCX2):​c.313G>A​(p.Ala105Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,208,454 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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. A105P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.000016 ( 0 hom. 7 hem. )

Consequence

ARMCX2
NM_177949.4 missense

Scores

1
16

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]

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=0.06939119).
BS2
High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARMCX2NM_177949.4 linkc.313G>A p.Ala105Thr 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>A p.Ala105Thr missense_variant Exon 6 of 6 1 NM_177949.4 ENSP00000349281.4 Q7L311

Frequencies

GnomAD3 genomes
AF:
0.0000353
AC:
4
AN:
113214
Hom.:
0
Cov.:
24
AF XY:
0.0000566
AC XY:
2
AN XY:
35352
show subpopulations
Gnomad AFR
AF:
0.000128
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:
0.0000220
AC:
4
AN:
181998
Hom.:
0
AF XY:
0.0000150
AC XY:
1
AN XY:
66630
show subpopulations
Gnomad AFR exome
AF:
0.0000762
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:
0.0000247
Gnomad OTH exome
AF:
0.000222
GnomAD4 exome
AF:
0.0000155
AC:
17
AN:
1095240
Hom.:
0
Cov.:
34
AF XY:
0.0000194
AC XY:
7
AN XY:
361090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000759
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:
0.0000179
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000353
AC:
4
AN:
113214
Hom.:
0
Cov.:
24
AF XY:
0.0000566
AC XY:
2
AN XY:
35352
show subpopulations
Gnomad4 AFR
AF:
0.000128
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:
0.0000416
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.313G>A (p.A105T) 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 313, causing the alanine (A) at amino acid position 105 to be replaced by a threonine (T). 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
0.068
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
4.4
DANN
Benign
0.82
DEOGEN2
Benign
0.029
T;T;T;T;T
FATHMM_MKL
Benign
0.087
N
LIST_S2
Benign
0.52
.;.;T;T;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.069
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N;N;N;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.52
N;N;N;N;N
REVEL
Benign
0.018
Sift
Benign
0.16
T;T;T;T;T
Sift4G
Uncertain
0.035
D;D;D;.;.
Polyphen
0.0070
B;B;B;.;.
Vest4
0.043
MutPred
0.26
Gain of glycosylation at A105 (P = 0.0042);Gain of glycosylation at A105 (P = 0.0042);Gain of glycosylation at A105 (P = 0.0042);Gain of glycosylation at A105 (P = 0.0042);Gain of glycosylation at A105 (P = 0.0042);
MVP
0.38
MPC
0.36
ClinPred
0.022
T
GERP RS
-0.14
Varity_R
0.040
gMVP
0.10

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; COSMIC: COSV57530743; COSMIC: COSV57530743; API