X-102602589-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001168478.2(ARMCX5):​c.448C>T​(p.Pro150Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,097,448 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )

Consequence

ARMCX5
NM_001168478.2 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.032454878).
BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARMCX5NM_001168478.2 linkc.448C>T p.Pro150Ser 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.448C>T p.Pro150Ser missense_variant Exon 4 of 4 2 NM_001168478.2 ENSP00000473737.2 Q6P1M9A0A0G2JLJ9

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000164
AC:
3
AN:
182755
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67501
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000157
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000729
AC:
8
AN:
1097448
Hom.:
0
Cov.:
31
AF XY:
0.00000827
AC XY:
3
AN XY:
362830
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000148
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.448C>T (p.P150S) 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 448, causing the proline (P) at amino acid position 150 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
0.085
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.0060
DANN
Benign
0.099
DEOGEN2
Benign
0.018
T;T;T
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.38
.;.;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.032
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L;L;L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.030
N;.;N
REVEL
Benign
0.013
Sift
Benign
0.71
T;.;T
Sift4G
Benign
0.52
T;T;T
Polyphen
0.020
B;B;B
Vest4
0.029
MutPred
0.17
Gain of phosphorylation at P150 (P = 0.0043);Gain of phosphorylation at P150 (P = 0.0043);Gain of phosphorylation at P150 (P = 0.0043);
MVP
0.082
MPC
0.12
ClinPred
0.027
T
GERP RS
-0.47
Varity_R
0.026
gMVP
0.091

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs750414266; hg19: chrX-101857517; API