X-101657084-C-T

Variant names:

• chrX-101657084-C-T
• NM_177949.4:c.505G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177949.4(ARMCX2):​c.505G>A​(p.Glu169Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ARMCX2 NM_177949.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.759

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]

ACMG classification

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=0.05551532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX2	NM_177949.4	c.505G>A	p.Glu169Lys	missense_variant	Exon 6 of 6	ENST00000356824.9	NP_808818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMCX2	ENST00000356824.9	c.505G>A	p.Glu169Lys	missense_variant	Exon 6 of 6	1	NM_177949.4	ENSP00000349281.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.505G>A (p.E169K) 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 505, causing the glutamic acid (E) at amino acid position 169 to be replaced by a lysine (K). 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	0.093
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.42
DEOGEN2	Benign	0.013	T;T;T
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.45	.;.;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.31	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.87	T;T;T
Polyphen		0.023	B;B;B
Vest4		0.057
MutPred		0.30		Gain of ubiquitination at E169 (P = 0.0114);Gain of ubiquitination at E169 (P = 0.0114);Gain of ubiquitination at E169 (P = 0.0114);
MVP		0.15
MPC		0.42
ClinPred		0.19	T
GERP RS		-4.9
Varity_R		0.069
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100912070;