rs10828395

Variant names:

• chr10-23008323-G-A
• rs10828395
• NM_173081.5:c.1877G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-23008323-G-A
• chr10-23008323-G-T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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: 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
• Publications: 21 publications found

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]

ENSG00000286924 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARMC3	NM_173081.5	c.1877G>A	p.Arg626Gln	missense_variant	Exon 15 of 19	ENST00000298032.10	NP_775104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC3	ENST00000298032.10	c.1877G>A	p.Arg626Gln	missense_variant	Exon 15 of 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

GnomAD2 exomes AF: 0.168 AC: 35522 AN: 211778 AF XY: 0.171

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 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

African (AFR) AF: 0.296 AC: 9286 AN: 31350

American (AMR) AF: 0.0877 AC: 3575 AN: 40770

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6024 AN: 24872

East Asian (EAS) AF: 0.113 AC: 4377 AN: 38696

South Asian (SAS) AF: 0.198 AC: 15700 AN: 79228

European-Finnish (FIN) AF: 0.149 AC: 7668 AN: 51406

Middle Eastern (MID) AF: 0.164 AC: 915 AN: 5596

European-Non Finnish (NFE) AF: 0.178 AC: 190286 AN: 1068076

Other (OTH) AF: 0.187 AC: 10765 AN: 57712

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

African (AFR) AF: 0.298 AC: 12340 AN: 41422

American (AMR) AF: 0.141 AC: 2153 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.121 AC: 630 AN: 5190

South Asian (SAS) AF: 0.195 AC: 941 AN: 4824

European-Finnish (FIN) AF: 0.147 AC: 1554 AN: 10578

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12333 AN: 67994

Other (OTH) AF: 0.189 AC: 400 AN: 2112

Alfa AF: 0.189 Hom.: 13732

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
PhyloP100		3.0
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10828395; hg19: chr10-23297252; COSMIC: COSV53059549;