Variant X-101624990-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_177947.3(ARMCX3):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,134,795 control chromosomes in the GnomAD database, including 1 homozygotes. There are 76 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00021 ( 1 hom. 70 hem. )

Consequence

ARMCX3
NM_177947.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

Variant links:

Genes affected

ARMCX3 (HGNC:24065): (armadillo repeat containing X-linked 3) This gene encodes a member of the ALEX family of proteins which may play a role in tumor suppression. The encoded protein contains a potential N-terminal transmembrane domain and a single Armadillo (arm) repeat. Other proteins containing the arm repeat are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is closely localized with other family members on the X chromosome. Three transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ARMCX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015531987).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARMCX3	NM_177947.3 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	5/5	ENST00000471229.7	NP_808816.1
ARMCX3	NM_016607.4 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	5/5		NP_057691.1
ARMCX3	NM_177948.3 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	5/5		NP_808817.1
ARMCX3	XM_005262141.4 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	5/5		XP_005262198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMCX3	ENST00000471229.7 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	5/5	1	NM_177947.3	ENSP00000454483	P1

Frequencies

GnomAD3 genomes

AF:

0.000196

AC:

AN:

111998

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34172

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.000667

GnomAD3 exomes

AF:

0.000224

AC:

AN:

125068

Hom.:

AF XY:

0.000252

AC XY:

AN XY:

39652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000198

Gnomad ASJ exome

AF:

0.00304

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000263

Gnomad OTH exome

AF:

0.000363

GnomAD4 exome

AF:

0.000207

AC:

212

AN:

1022744

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

325524

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.000178

Gnomad4 ASJ exome

AF:

0.00460

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000929

Gnomad4 OTH exome

AF:

0.000585

GnomAD4 genome

AF:

0.000196

AC:

AN:

112051

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34235

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00415

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.000658

Alfa

AF:

0.000433

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000224

AC:

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

Aug 30, 2021

The c.11C>T (p.A4V) alteration is located in exon 5 (coding exon 1) of the ARMCX3 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.019

T;T;T;.;T

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.60

.;.;T;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.016

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

N;N;.;.;N

MutationTaster

Benign

0.86

N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.45

N;N;N;N;N

REVEL

Benign

0.059

Sift

Benign

0.95

T;T;T;T;T

Sift4G

Benign

0.10

T;T;T;T;T

Polyphen

0.81

P;P;.;.;P

Vest4

0.32

MVP

0.92

MPC

0.92

ClinPred

0.053

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.087

gMVP

0.17

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