10-22959121-C-A

Position:

• chr10-22959121-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173081.5(ARMC3):​c.344C>A​(p.Ala115Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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)
• Consequence: ARMC3 NM_173081.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3163067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC3	NM_173081.5	c.344C>A	p.Ala115Asp	missense_variant	5/19	ENST00000298032.10	NP_775104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC3	ENST00000298032.10	c.344C>A	p.Ala115Asp	missense_variant	5/19	1	NM_173081.5	ENSP00000298032.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.344C>A (p.A115D) alteration is located in exon 5 (coding exon 4) of the ARMC3 gene. This alteration results from a C to A substitution at nucleotide position 344, causing the alanine (A) at amino acid position 115 to be replaced by an aspartic acid (D). 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	0.17
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.0091	T;.;.;T
Eigen	Benign	-0.043
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D;D;D;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L;L;L;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.20	T;T;T;T
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;B;.;B
Vest4		0.53
MutPred		0.43		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;
MVP		0.72
MPC		0.50
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.35
gMVP		0.26

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

Other links and lift over

dbSNP: rs961408205; hg19: chr10-23248050;