Variant 10-22962058-A-G 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_173081.5(ARMC3):c.712A>G(p.Ile238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,577,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ARMC3
NM_173081.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.325

Variant links:

Genes affected

ARMC3 (HGNC:30964): (armadillo repeat containing 3) Armadillo/beta-catenin (CTNNB1; MIM 116806)-like (ARM) domains are imperfect 45-amino acid repeats involved in protein-protein interactions. ARM domain-containing proteins, such as ARMC3, function in signal transduction, development, cell adhesion and mobility, and tumor initiation and metastasis (Li et al., 2006 [PubMed 16915934]).[supplied by OMIM, Mar 2008]

ARMC3 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=0.043111235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC3	NM_173081.5 linkuse as main transcript	c.712A>G	p.Ile238Val	missense_variant	7/19	ENST00000298032.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC3	ENST00000298032.10 linkuse as main transcript	c.712A>G	p.Ile238Val	missense_variant	7/19	1	NM_173081.5	A1	Q5W041-2

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000486

AC:

AN:

226570

Hom.:

AF XY:

0.0000569

AC XY:

AN XY:

123042

show subpopulations

Gnomad AFR exome

AF:

0.000648

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:

0.00000935

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1425084

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

706302

show subpopulations

Gnomad4 AFR exome

AF:

0.000566

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.13e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000204

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000724

Gnomad4 AMR

AF:

0.0000654

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

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

Dec 06, 2021

The c.712A>G (p.I238V) alteration is located in exon 7 (coding exon 6) of the ARMC3 gene. This alteration results from a A to G substitution at nucleotide position 712, causing the isoleucine (I) at amino acid position 238 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

Benign

0.084

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Benign

0.70

DEOGEN2

Benign

0.0018

T;.;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.35

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.73

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.20

B;B;.

Vest4

0.29

MVP

0.22

MPC

0.14

ClinPred

0.016

GERP RS

0.39

Varity_R

0.037

gMVP

0.083

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