10-23002023-C-T

Position:

• chr10-23002023-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_173081.5(ARMC3):​c.1530C>T​(p.Asp510Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,613,624 control chromosomes in the GnomAD database, including 3,034 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (570 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2464 hom.)
• Consequence: ARMC3 NM_173081.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.399 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC3	NM_173081.5	c.1530C>T	p.Asp510Asp	synonymous_variant	12/19	ENST00000298032.10	NP_775104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC3	ENST00000298032.10	c.1530C>T	p.Asp510Asp	synonymous_variant	12/19	1	NM_173081.5	ENSP00000298032.5

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11379 AN: 152082 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0704

GnomAD3 exomes AF: 0.0525 AC: 13153 AN: 250588 Hom.: 494 AF XY: 0.0524 AC XY: 7095 AN XY: 135424

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.0527

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0510

Gnomad FIN exome AF: 0.0634

Gnomad NFE exome AF: 0.0560

Gnomad OTH exome AF: 0.0482

GnomAD4 exome AF: 0.0541 AC: 79075 AN: 1461424 Hom.: 2464 Cov.: 31 AF XY: 0.0539 AC XY: 39190 AN XY: 727028

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0272

Gnomad4 ASJ exome AF: 0.0535

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0503

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.0542

Gnomad4 OTH exome AF: 0.0557

GnomAD4 genome AF: 0.0748 AC: 11391 AN: 152200 Hom.: 570 Cov.: 32 AF XY: 0.0724 AC XY: 5388 AN XY: 74426

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0634

Gnomad4 NFE AF: 0.0558

Gnomad4 OTH AF: 0.0692

Alfa AF: 0.0544 Hom.: 318

Bravo AF: 0.0752

Asia WGS AF: 0.0380 AC: 134 AN: 3478

EpiCase AF: 0.0592

EpiControl AF: 0.0555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.24
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12259839; hg19: chr10-23290952; COSMIC: COSV53062260; COSMIC: COSV53062260;