Variant X-102602427-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001168478.2(ARMCX5):c.286C>T(p.Pro96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 111,999 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Consequence

ARMCX5
NM_001168478.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.212

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03777212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX5	NM_001168478.2 linkuse as main transcript	c.286C>T	p.Pro96Ser	missense_variant	4/4	ENST00000473968.7	NP_001161950.1
ARMCX5-GPRASP2	NR_146584.3 linkuse as main transcript	n.477+450C>T		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.286C>T	p.Pro96Ser	missense_variant	4/4	2	NM_001168478.2	ENSP00000473737	P1
	ENST00000602441.1 linkuse as main transcript	n.129-2512G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111999

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34177

show subpopulations

Gnomad AFR

AF:

0.0000650

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111999

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34177

show subpopulations

Gnomad4 AFR

AF:

0.0000650

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain: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

Oct 12, 2021

The c.286C>T (p.P96S) 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 286, causing the proline (P) at amino acid position 96 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

0.074

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.2

DANN

Benign

0.33

DEOGEN2

Benign

0.018

T;T;T

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.41

.;.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

0.31

N;.;N

REVEL

Benign

0.017

Sift

Benign

0.32

T;.;T

Sift4G

Benign

0.80

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.029

MutPred

0.18

Gain of phosphorylation at P96 (P = 0.0573);Gain of phosphorylation at P96 (P = 0.0573);Gain of phosphorylation at P96 (P = 0.0573);

MVP

0.068

MPC

0.12

ClinPred

0.056

GERP RS

-0.76

Varity_R

0.027

gMVP

0.053

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