10-23002023-C-T

Variant names:

• chr10-23002023-C-T
• rs12259839
• NM_173081.5:c.1530C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173081.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC3	NM_173081.5	MANE Select	c.1530C>T	p.Asp510Asp	synonymous	Exon 12 of 19	NP_775104.2	Q5W041-2
	ARMC3	NM_001282745.2		c.1530C>T	p.Asp510Asp	synonymous	Exon 12 of 19	NP_001269674.1	Q5W041-4
	ARMC3	NM_001282746.2		c.1530C>T	p.Asp510Asp	synonymous	Exon 12 of 17	NP_001269675.1	Q5W041-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC3	ENST00000298032.10	TSL:1 MANE Select	c.1530C>T	p.Asp510Asp	synonymous	Exon 12 of 19	ENSP00000298032.5	Q5W041-2
	ARMC3	ENST00000409049.7	TSL:1	c.1530C>T	p.Asp510Asp	synonymous	Exon 12 of 17	ENSP00000387288.3	Q5W041-3
	ARMC3	ENST00000409983.7	TSL:2	c.1530C>T	p.Asp510Asp	synonymous	Exon 12 of 19	ENSP00000386943.3	Q5W041-4

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

GnomAD2 exomes AF: 0.0525 AC: 13153 AN: 250588 AF XY: 0.0524

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 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

African (AFR) AF: 0.141 AC: 4723 AN: 33456

American (AMR) AF: 0.0272 AC: 1218 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0535 AC: 1397 AN: 26120

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39684

South Asian (SAS) AF: 0.0503 AC: 4338 AN: 86220

European-Finnish (FIN) AF: 0.0625 AC: 3338 AN: 53410

Middle Eastern (MID) AF: 0.0747 AC: 429 AN: 5740

European-Non Finnish (NFE) AF: 0.0542 AC: 60258 AN: 1111736

Other (OTH) AF: 0.0557 AC: 3360 AN: 60360

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

African (AFR) AF: 0.138 AC: 5738 AN: 41516

American (AMR) AF: 0.0347 AC: 531 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4822

European-Finnish (FIN) AF: 0.0634 AC: 672 AN: 10594

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0558 AC: 3798 AN: 68004

Other (OTH) AF: 0.0692 AC: 146 AN: 2110

Alfa AF: 0.0574 Hom.: 441

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.24
DANN	Benign	0.84
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12259839; hg19: chr10-23290952; COSMIC: COSV53062260; COSMIC: COSV53062260;