rs11013233

Positions:

• chr10-23006974-T-C

Variant summary

Our verdict is Benign. Variant got -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. 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 0.031 (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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ARMC3	NM_173081.5	c.1822T>C	p.Ser608Pro	missense_variant	14/19	ENST00000298032.10
LOC107984215	XR_001747394.2	n.555-11156A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC3	ENST00000298032.10	c.1822T>C	p.Ser608Pro	missense_variant	14/19	1	NM_173081.5	A1
	ENST00000655462.1	n.117-40656A>G		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.0383 AC: 9369 AN: 244700 Hom.: 239 AF XY: 0.0408 AC XY: 5403 AN XY: 132278

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 SAS exome AF: 0.0612

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

Gnomad4 AFR exome AF: 0.00614

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0582

Gnomad4 FIN exome AF: 0.0499

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.0435

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

Gnomad4 AFR AF: 0.00758

Gnomad4 AMR AF: 0.0308

Gnomad4 ASJ AF: 0.0999

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0501

Gnomad4 NFE AF: 0.0406

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0399 Hom.: 309

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
MutationTaster	Benign	0.99	N;N;N;N;N
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
Polyphen		0.0010	B;.;B;.
Vest4		0.13
MPC		0.13
ClinPred		0.0055	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.39

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