NM_177949.4:c.835C>A

Variant names:

• chrX-101656754-G-T
• rs1240818240
• NM_177949.4:c.835C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_177949.4(ARMCX2):​c.835C>A​(p.Pro279Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,281 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ARMCX2 NM_177949.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.867
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18055165).

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.835C>A	p.Pro279Thr	missense	Exon 6 of 6	NP_808818.1	Q7L311
	ARMCX2	NM_001282231.2		c.835C>A	p.Pro279Thr	missense	Exon 6 of 6	NP_001269160.1	Q7L311
	ARMCX2	NM_014782.7		c.835C>A	p.Pro279Thr	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.835C>A	p.Pro279Thr	missense	Exon 6 of 6	ENSP00000349281.4	Q7L311
	ARMCX2	ENST00000328766.9	TSL:1	c.835C>A	p.Pro279Thr	missense	Exon 5 of 5	ENSP00000331662.5	Q7L311
	ARMCX2	ENST00000330154.6	TSL:1	c.835C>A	p.Pro279Thr	missense	Exon 3 of 3	ENSP00000328631.2	Q7L311

Frequencies

GnomAD3 genomes AF: 0.00000901 AC: 1 AN: 111024 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000949

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: 9.11e-7 AC: 1 AN: 1098257 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363611

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.0000284 AC: 1 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842146

Other (OTH) AF: 0.00 AC: 0 AN: 46098

GnomAD4 genome AF: 0.00000901 AC: 1 AN: 111024 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 33214

African (AFR) AF: 0.00 AC: 0 AN: 30513

American (AMR) AF: 0.0000949 AC: 1 AN: 10535

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3516

South Asian (SAS) AF: 0.00 AC: 0 AN: 2569

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52860

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.87
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.051	T
Polyphen		1.0	D
Vest4		0.18
MutPred		0.33		Gain of phosphorylation at P279 (P = 0.0339)
MVP		0.49
MPC		0.97
ClinPred		0.56	D
GERP RS		2.5
Varity_R		0.17
gMVP		0.51
Mutation Taster		=98/2	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: rs1240818240; hg19: chrX-100911740;