chrX-102602314-C-A

Variant names:

• chrX-102602314-C-A
• NM_001168478.2:c.173C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001168478.2(ARMCX5):​c.173C>A​(p.Ala58Glu) 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. 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. A58V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ARMCX5 NM_001168478.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683

Genes affected

ARMCX5 (HGNC:25772): (armadillo repeat containing X-linked 5)

ARMCX5-GPRASP2 (HGNC:):

ARMCX5-GPRASP2 (HGNC:42000): (ARMCX5-GPRASP2 readthrough) This locus represents naturally occurring readthrough transcription among the adjacent armadillo repeat containing, X-linked 5 (ARMCX5), G protein-coupled receptor associated sorting proteins 1 and 2 (GPRASP1 and GPRASP2), basic helix-loop-helix family member b9 (BHLHB9), and long intergenic non-protein coding RNA 630 (LINC00630) genes on chromosome X. Transcripts may make use of multiple alternative promoters and polyadenylation signals in this region. Readthrough transcripts may produce proteins identical to the proteins encoded by GPRASP2 or BHLHB9. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0801577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX5	NM_001168478.2	c.173C>A	p.Ala58Glu	missense_variant	Exon 4 of 4	ENST00000473968.7	NP_001161950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMCX5	ENST00000473968.7	c.173C>A	p.Ala58Glu	missense_variant	Exon 4 of 4	2	NM_001168478.2	ENSP00000473737.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.5
DANN	Benign	0.85
DEOGEN2	Benign	0.032	T;T;.;.;T
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.37	.;.;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.080	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;.;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N;.;.;.;N
REVEL	Benign	0.043
Sift	Uncertain	0.0040	D;.;.;.;D
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		0.84	P;P;.;.;P
Vest4		0.31
MutPred		0.20		Loss of MoRF binding (P = 0.0324);Loss of MoRF binding (P = 0.0324);Loss of MoRF binding (P = 0.0324);Loss of MoRF binding (P = 0.0324);Loss of MoRF binding (P = 0.0324);
MVP		0.082
MPC		0.17
ClinPred		0.20	T
GERP RS		1.9
Varity_R		0.16
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-101857242;