rs11013233

Variant names:

• chr10-23006974-T-C
• rs11013233
• NM_173081.5:c.1822T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173081.5(ARMC3):​c.1822T>C​(p.Ser608Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,605,986 control chromosomes in the GnomAD database, including 1,516 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 0.031 (105 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1411 hom.)
• Consequence: ARMC3 NM_173081.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 14 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=0.0016603768).
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC3	NM_173081.5	c.1822T>C	p.Ser608Pro	missense_variant	Exon 14 of 19	ENST00000298032.10	NP_775104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC3	ENST00000298032.10	c.1822T>C	p.Ser608Pro	missense_variant	Exon 14 of 19	1	NM_173081.5	ENSP00000298032.5

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4777 AN: 152158 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.00760

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0999

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0383 AC: 9369 AN: 244700 AF XY: 0.0408

Gnomad AFR exome AF: 0.00712

Gnomad AMR exome AF: 0.0203

Gnomad ASJ exome AF: 0.0984

Gnomad EAS exome AF: 0.000275

Gnomad FIN exome AF: 0.0493

Gnomad NFE exome AF: 0.0409

Gnomad OTH exome AF: 0.0437

GnomAD4 exome AF: 0.0406 AC: 58998 AN: 1453710 Hom.: 1411 Cov.: 30 AF XY: 0.0415 AC XY: 30029 AN XY: 723158

African (AFR) AF: 0.00614 AC: 203 AN: 33050

American (AMR) AF: 0.0209 AC: 908 AN: 43482

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2629 AN: 25670

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39636

South Asian (SAS) AF: 0.0582 AC: 4949 AN: 85090

European-Finnish (FIN) AF: 0.0499 AC: 2652 AN: 53096

Middle Eastern (MID) AF: 0.0427 AC: 245 AN: 5732

European-Non Finnish (NFE) AF: 0.0404 AC: 44793 AN: 1107926

Other (OTH) AF: 0.0435 AC: 2614 AN: 60028

GnomAD4 genome AF: 0.0314 AC: 4778 AN: 152276 Hom.: 105 Cov.: 32 AF XY: 0.0326 AC XY: 2427 AN XY: 74460

African (AFR) AF: 0.00758 AC: 315 AN: 41566

American (AMR) AF: 0.0308 AC: 472 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 346 AN: 3464

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4824

European-Finnish (FIN) AF: 0.0501 AC: 531 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0406 AC: 2763 AN: 68022

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0379 Hom.: 409

Bravo AF: 0.0278

TwinsUK AF: 0.0429 AC: 159

ALSPAC AF: 0.0394 AC: 152

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.0403 AC: 347

ExAC AF: 0.0367 AC: 4461

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00089	T;T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.56	T;T;T;T
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;L;L
PhyloP100		1.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.080	N;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.090	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Vest4		0.13
ClinPred		0.0055	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.39
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11013233; hg19: chr10-23295903; COSMIC: COSV53066771;