chr10-22961004-C-T

Position:

• chr10-22961004-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173081.5(ARMC3):​c.538-880C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,076 control chromosomes in the GnomAD database, including 34,540 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 0.65 (34533 hom., cov: 31)
  • Exomes 𝑓: 0.56 (7 hom.)
• Consequence: ARMC3 NM_173081.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC3	NM_173081.5	c.538-880C>T		intron_variant		ENST00000298032.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC3	ENST00000298032.10	c.538-880C>T		intron_variant		1	NM_173081.5	A1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99420 AN: 151906 Hom.: 34483 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.558 AC: 29 AN: 52 Hom.: 7 Cov.: 0 AF XY: 0.611 AC XY: 22 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.655 AC: 99534 AN: 152024 Hom.: 34533 Cov.: 31 AF XY: 0.654 AC XY: 48539 AN XY: 74270

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.613

Alfa AF: 0.616 Hom.: 3537

Bravo AF: 0.672

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.5
DANN	Benign	0.20

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: rs1171141; hg19: chr10-23249933;