chr10-23008323-G-A

Position:

• chr10-23008323-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173081.5(ARMC3):​c.1877G>A​(p.Arg626Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,549,776 control chromosomes in the GnomAD database, including 26,762 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (3597 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23165 hom.)
• Consequence: ARMC3 NM_173081.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035220385).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC3	NM_173081.5	c.1877G>A	p.Arg626Gln	missense_variant	15/19	ENST00000298032.10	NP_775104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC3	ENST00000298032.10	c.1877G>A	p.Arg626Gln	missense_variant	15/19	1	NM_173081.5	ENSP00000298032.5

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31439 AN: 151952 Hom.: 3589 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.168 AC: 35522 AN: 211778 Hom.: 3266 AF XY: 0.171 AC XY: 19447 AN XY: 113732

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.0811

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.117

Gnomad SAS exome AF: 0.198

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.178 AC: 248596 AN: 1397706 Hom.: 23165 Cov.: 27 AF XY: 0.179 AC XY: 124588 AN XY: 694748

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.207 AC: 31476 AN: 152070 Hom.: 3597 Cov.: 32 AF XY: 0.205 AC XY: 15220 AN XY: 74346

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.189

Alfa AF: 0.186 Hom.: 7009

Bravo AF: 0.210

TwinsUK AF: 0.184 AC: 684

ALSPAC AF: 0.175 AC: 676

ESP6500AA AF: 0.273 AC: 1197

ESP6500EA AF: 0.181 AC: 1544

ExAC AF: 0.163 AC: 19356

Asia WGS AF: 0.185 AC: 641 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00036	T;T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;T;T;T
MetaRNN	Benign	0.0035	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.12	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.45	T;T;T;T
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.29	B;.;B;.
Vest4		0.089
MPC		0.12
ClinPred		0.018	T
GERP RS		5.6
Varity_R		0.082
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10828395; hg19: chr10-23297252; COSMIC: COSV53059549;