chrX-102602651-A-G

Variant names:

• chrX-102602651-A-G
• NM_001168478.2:c.510A>G

Variant summary

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

The NM_001168478.2(ARMCX5):​c.510A>G​(p.Ile170Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,684 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: ARMCX5 NM_001168478.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00900
• Publications: 0 publications found

Genes affected

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

ENSG00000271147 (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

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=0.070080966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168478.2. 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
	ARMCX5	NM_001168478.2	MANE Select	c.510A>G	p.Ile170Met	missense	Exon 4 of 4	NP_001161950.1	Q6P1M9
	ARMCX5	NM_001168479.2		c.510A>G	p.Ile170Met	missense	Exon 6 of 6	NP_001161951.1	Q6P1M9
	ARMCX5	NM_001168480.2		c.510A>G	p.Ile170Met	missense	Exon 6 of 6	NP_001161952.1	Q6P1M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX5	ENST00000473968.7	TSL:2 MANE Select	c.510A>G	p.Ile170Met	missense	Exon 4 of 4	ENSP00000473737.2	Q6P1M9
	ARMCX5	ENST00000479502.2	TSL:1	c.510A>G	p.Ile170Met	missense	Exon 3 of 3	ENSP00000474470.2	Q6P1M9
	ENSG00000271147	ENST00000466616.6	TSL:1	n.466+674A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097684 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363062

African (AFR) AF: 0.00 AC: 0 AN: 26386

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40527

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841624

Other (OTH) AF: 0.00 AC: 0 AN: 46083

GnomAD4 genome Cov.: 23

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	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.63
DEOGEN2	Benign	0.034	T
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.0090
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.030
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.028	D
Polyphen		0.42	B
Vest4		0.17
MutPred		0.31		Gain of disorder (P = 0.0332)
MVP		0.043
MPC		0.19
ClinPred		0.095	T
GERP RS		0.43
Varity_R		0.15
gMVP		0.040
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

hg19: chrX-101857579; COSMIC: COSV55767035; COSMIC: COSV55767035;