chrX-101657225-C-T

Variant names:

• chrX-101657225-C-T
• rs144651046
• NM_177949.4:c.364G>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.364G>A​(p.Gly122Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G122W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 1 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: ARMCX2 NM_177949.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.14
• 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=0.040530443).

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.364G>A	p.Gly122Arg	missense	Exon 6 of 6	NP_808818.1	Q7L311
	ARMCX2	NM_001282231.2		c.364G>A	p.Gly122Arg	missense	Exon 6 of 6	NP_001269160.1	Q7L311
	ARMCX2	NM_014782.7		c.364G>A	p.Gly122Arg	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.364G>A	p.Gly122Arg	missense	Exon 6 of 6	ENSP00000349281.4	Q7L311
	ARMCX2	ENST00000328766.9	TSL:1	c.364G>A	p.Gly122Arg	missense	Exon 5 of 5	ENSP00000331662.5	Q7L311
	ARMCX2	ENST00000330154.6	TSL:1	c.364G>A	p.Gly122Arg	missense	Exon 3 of 3	ENSP00000328631.2	Q7L311

Frequencies

GnomAD3 genomes AF: 0.00000883 AC: 1 AN: 113260 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

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: 0.0000187

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000883 AC: 1 AN: 113260 Hom.: 0 Cov.: 24 AF XY: 0.0000282 AC XY: 1 AN XY: 35404

African (AFR) AF: 0.00 AC: 0 AN: 31241

American (AMR) AF: 0.00 AC: 0 AN: 10870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3568

South Asian (SAS) AF: 0.00 AC: 0 AN: 2785

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000187 AC: 1 AN: 53340

Other (OTH) AF: 0.00 AC: 0 AN: 1535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.79
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		-4.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.010
Sift	Benign	0.11	T
Sift4G	Benign	0.084	T
Polyphen		0.0030	B
Vest4		0.052
MutPred		0.36		Loss of catalytic residue at V123 (P = 0.0409)
MVP		0.12
MPC		0.44
ClinPred		0.080	T
GERP RS		-7.9
Varity_R		0.094
gMVP		0.11
Mutation Taster		=100/0	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

dbSNP: rs144651046; hg19: chrX-100912211; COSMIC: COSV57529695; COSMIC: COSV57529695;