Genetic Variant ARMC3:p.Arg626Leu (chr10-23008323-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173081.5(ARMC3):c.1877G>T(p.Arg626Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARMC3
NM_173081.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.02

Publications

21 publications found

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:

ENSG00000286924 (HGNC:):

ENSG00000286924 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173081.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARMC3	NM_173081.5	MANE Select	c.1877G>T	p.Arg626Leu	missense	Exon 15 of 19	NP_775104.2
ARMC3	NM_001282745.2		c.1877G>T	p.Arg626Leu	missense	Exon 15 of 19	NP_001269674.1
ARMC3	NM_001282746.2		c.1877G>T	p.Arg626Leu	missense	Exon 15 of 17	NP_001269675.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARMC3	ENST00000298032.10	TSL:1 MANE Select	c.1877G>T	p.Arg626Leu	missense	Exon 15 of 19	ENSP00000298032.5
ARMC3	ENST00000409049.7	TSL:1	c.1877G>T	p.Arg626Leu	missense	Exon 15 of 17	ENSP00000387288.3
ARMC3	ENST00000409983.7	TSL:2	c.1877G>T	p.Arg626Leu	missense	Exon 15 of 19	ENSP00000386943.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1402722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697268

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

40892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24948

East Asian (EAS)

AF:

0.00

AC:

AN:

38776

South Asian (SAS)

AF:

0.00

AC:

AN:

79476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072008

Other (OTH)

AF:

0.00

AC:

AN:

57920

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.00093

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

M_CAP

Benign

0.011

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

PhyloP100

3.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.88

REVEL

Benign

0.12

Sift

Benign

0.095

Sift4G

Benign

0.55

Polyphen

0.93

Vest4

0.42

MutPred

0.32

Loss of MoRF binding (P = 0.0152)

MVP

0.69

MPC

0.37

ClinPred

0.89

GERP RS

5.6

Varity_R

0.13

gMVP

0.48

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: -47

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over