chrX-101657159-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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

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 -6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX2	NM_177949.4	c.430G>T	p.Gly144Trp	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.430G>T	p.Gly144Trp	missense_variant	Exon 6 of 6	1	NM_177949.4	ENSP00000349281.4

Frequencies

GnomAD3 genomes AF: 0.0000442 AC: 5 AN: 113063 Hom.: 0 Cov.: 24 AF XY: 0.0000284 AC XY: 1 AN XY: 35207

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

GnomAD3 exomes AF: 0.0000124 AC: 2 AN: 161532 Hom.: 0 AF XY: 0.0000189 AC XY: 1 AN XY: 52864

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 SAS 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

Gnomad4 AFR exome AF: 0.0000786

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000651

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0000321

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000751

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000896 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 v4.3

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;T;T;T;T
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.36	.;.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.072	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L;L;L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.070	T;T;T;T;T
Sift4G	Benign	0.083	T;T;T;.;.
Polyphen		0.0020	B;B;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

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

LitVar

Other links and lift over

dbSNP: rs149321969; hg19: chrX-100912145;