NM_177949.4:c.430G>T

Variant names:

• chrX-101657159-C-A
• rs149321969
• NM_177949.4:c.430G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_177949.4(ARMCX2):​c.430G>T​(p.Gly144Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,186,741 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. 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. G144R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000052 (0 hom. 24 hem.)
• Consequence: ARMCX2 NM_177949.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07232013).
• BS2: High Hemizygotes in GnomAdExome4 at 24 gene

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.430G>T	p.Gly144Trp	missense	Exon 6 of 6	NP_808818.1	Q7L311
	ARMCX2	NM_001282231.2		c.430G>T	p.Gly144Trp	missense	Exon 6 of 6	NP_001269160.1	Q7L311
	ARMCX2	NM_014782.7		c.430G>T	p.Gly144Trp	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.430G>T	p.Gly144Trp	missense	Exon 6 of 6	ENSP00000349281.4	Q7L311
	ARMCX2	ENST00000328766.9	TSL:1	c.430G>T	p.Gly144Trp	missense	Exon 5 of 5	ENSP00000331662.5	Q7L311
	ARMCX2	ENST00000330154.6	TSL:1	c.430G>T	p.Gly144Trp	missense	Exon 3 of 3	ENSP00000328631.2	Q7L311

Frequencies

GnomAD3 genomes AF: 0.0000442 AC: 5 AN: 113063 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000321

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: 0.0000751

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000124 AC: 2 AN: 161532 AF XY: 0.0000189

Gnomad AFR exome AF: 0.0000798

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000135

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000522 AC: 56 AN: 1073678 Hom.: 0 Cov.: 33 AF XY: 0.0000691 AC XY: 24 AN XY: 347364

African (AFR) AF: 0.0000786 AC: 2 AN: 25433

American (AMR) AF: 0.00 AC: 0 AN: 31303

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17864

East Asian (EAS) AF: 0.00 AC: 0 AN: 29861

South Asian (SAS) AF: 0.00 AC: 0 AN: 51223

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4001

European-Non Finnish (NFE) AF: 0.0000651 AC: 54 AN: 829455

Other (OTH) AF: 0.00 AC: 0 AN: 44770

GnomAD4 genome AF: 0.0000442 AC: 5 AN: 113063 Hom.: 0 Cov.: 24 AF XY: 0.0000284 AC XY: 1 AN XY: 35207

African (AFR) AF: 0.0000321 AC: 1 AN: 31156

American (AMR) AF: 0.00 AC: 0 AN: 10843

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 2800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000751 AC: 4 AN: 53294

Other (OTH) AF: 0.00 AC: 0 AN: 1532

Alfa AF: 0.000122 Hom.: 2

Bravo AF: 0.0000227

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.035
DANN	Benign	0.32
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.77
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.057
Sift	Benign	0.070	T
Sift4G	Benign	0.083	T
Polyphen		0.0020	B
Vest4		0.20
MVP		0.13
MPC		0.44
ClinPred		0.050	T
GERP RS		-9.6
Varity_R		0.037
gMVP		0.11
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

dbSNP: rs149321969; hg19: chrX-100912145;