X-102602943-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.618
Variant links:
Genes affected
ARMCX5 (HGNC:25772): (armadillo repeat containing X-linked 5)
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]

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ACMG classification

Classification made for transcript

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
ARMCX5NM_001168478.2 linkc.802C>T p.Pro268Ser missense_variant Exon 4 of 4 ENST00000473968.7 NP_001161950.1 Q6P1M9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARMCX5ENST00000473968.7 linkc.802C>T p.Pro268Ser missense_variant Exon 4 of 4 2 NM_001168478.2 ENSP00000473737.2 Q6P1M9A0A0G2JLJ9

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
LINK: link

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; API