X-102602943-C-T

Variant names:

• chrX-102602943-C-T
• NM_001168478.2:c.802C>T

Variant summary

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

The NM_001168478.2(ARMCX5):​c.802C>T​(p.Pro268Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ARMCX5 NM_001168478.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.618

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=0.2464951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX5	NM_001168478.2	c.802C>T	p.Pro268Ser	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.802C>T	p.Pro268Ser	missense_variant	Exon 4 of 4	2	NM_001168478.2	ENSP00000473737.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 05, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.802C>T (p.P268S) alteration is located in exon 6 (coding exon 1) of the ARMCX5 gene. This alteration results from a C to T substitution at nucleotide position 802, causing the proline (P) at amino acid position 268 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.62	.;.;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.3	D;.;D
REVEL	Benign	0.038
Sift	Uncertain	0.013	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.90	P;P;P
Vest4		0.23
MutPred		0.45		Loss of catalytic residue at P268 (P = 1e-04);Loss of catalytic residue at P268 (P = 1e-04);Loss of catalytic residue at P268 (P = 1e-04);
MVP		0.15
MPC		0.56
ClinPred		0.89	D
GERP RS		2.8
Varity_R		0.28
gMVP		0.61

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-101857871;