chrX-101657084-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 15/21 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
• Publications: 0 publications found

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

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=0.05551532).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX2	NM_177949.4	MANE Select	c.505G>A	p.Glu169Lys	missense	Exon 6 of 6	NP_808818.1	Q7L311
	ARMCX2	NM_001282231.2		c.505G>A	p.Glu169Lys	missense	Exon 6 of 6	NP_001269160.1	Q7L311
	ARMCX2	NM_014782.7		c.505G>A	p.Glu169Lys	missense	Exon 5 of 5	NP_055597.1	Q7L311

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX2	ENST00000356824.9	TSL:1 MANE Select	c.505G>A	p.Glu169Lys	missense	Exon 6 of 6	ENSP00000349281.4	Q7L311
	ARMCX2	ENST00000328766.9	TSL:1	c.505G>A	p.Glu169Lys	missense	Exon 5 of 5	ENSP00000331662.5	Q7L311
	ARMCX2	ENST00000330154.6	TSL:1	c.505G>A	p.Glu169Lys	missense	Exon 3 of 3	ENSP00000328631.2	Q7L311

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.76
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.050
Sift	Benign	0.27	T
Sift4G	Benign	0.87	T
Polyphen		0.023	B
Vest4		0.057
MutPred		0.30		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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chrX-100912070;