10-22961004-C-T

Variant names:

• chr10-22961004-C-T
• rs1171141
• NM_173081.5:c.538-880C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARMC3	NM_173081.5	c.538-880C>T		intron_variant	Intron 6 of 18	ENST00000298032.10	NP_775104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC3	ENST00000298032.10	c.538-880C>T		intron_variant	Intron 6 of 18	1	NM_173081.5	ENSP00000298032.5

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 18 AN: 36

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.908 AC: 37679 AN: 41502

American (AMR) AF: 0.626 AC: 9571 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2052 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2557 AN: 5160

South Asian (SAS) AF: 0.541 AC: 2602 AN: 4810

European-Finnish (FIN) AF: 0.540 AC: 5696 AN: 10542

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.551 AC: 37445 AN: 67952

Other (OTH) AF: 0.613 AC: 1291 AN: 2106

Alfa AF: 0.616 Hom.: 3568

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
PhyloP100		0.081
Mutation Taster		=100/0	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: rs1171141; hg19: chr10-23249933;