X-102603275-C-G

Position:

chrX-102603275-C-G

Variant summary

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

The NM_001168478.2(ARMCX5):c.1134C>G(p.Asp378Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000984 in 1,209,380 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 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: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000097 ( 0 hom. 27 hem. )

Consequence

ARMCX5
NM_001168478.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -2.01

Variant links:

Genes affected

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

ARMCX5 links:

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]

ARMCX5-GPRASP2 links:

(HGNC:):

links:

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=0.030343413).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX5	NM_001168478.2 linkuse as main transcript	c.1134C>G	p.Asp378Glu	missense_variant	4/4	ENST00000473968.7	NP_001161950.1
ARMCX5-GPRASP2	NR_146584.3 linkuse as main transcript	n.477+1298C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMCX5	ENST00000473968.7 linkuse as main transcript	c.1134C>G	p.Asp378Glu	missense_variant	4/4	2	NM_001168478.2	ENSP00000473737	P1
	ENST00000602441.1 linkuse as main transcript	n.129-3360G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

111479

Hom.:

Cov.:

AF XY:

0.0000891

AC XY:

AN XY:

33661

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000226

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

182633

Hom.:

AF XY:

0.0000891

AC XY:

AN XY:

67351

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000975

AC:

107

AN:

1097901

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

363275

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.000108

AC:

AN:

111479

Hom.:

Cov.:

AF XY:

0.0000891

AC XY:

AN XY:

33661

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.1134C>G (p.D378E) alteration is located in exon 6 (coding exon 1) of the ARMCX5 gene. This alteration results from a C to G substitution at nucleotide position 1134, causing the aspartic acid (D) at amino acid position 378 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

ARMCX5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 20, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.012

DANN

Benign

0.16

DEOGEN2

Benign

0.023

T;T;T

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.41

.;.;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.11

N;.;N

REVEL

Benign

0.014

Sift

Benign

0.79

T;.;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.055

MutPred

0.67

Loss of glycosylation at S383 (P = 0.2463);Loss of glycosylation at S383 (P = 0.2463);Loss of glycosylation at S383 (P = 0.2463);

MVP

0.15

MPC

0.11

ClinPred

0.029

GERP RS

-6.4

Varity_R

0.047

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over