3-138252065-G-A

Position:

• chr3-138252065-G-A

Variant summary

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

The NM_001363941.2(ARMC8):​c.1134+6882G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,022 control chromosomes in the GnomAD database, including 18,972 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 0.47 (18972 hom., cov: 32)
• Consequence: ARMC8 NM_001363941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

Genes affected

ARMC8 (HGNC:24999): (armadillo repeat containing 8) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC8	NM_001363941.2	c.1134+6882G>A		intron_variant		ENST00000469044.6	NP_001350870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC8	ENST00000469044.6	c.1134+6882G>A		intron_variant		5	NM_001363941.2	ENSP00000419413	P1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71036 AN: 151904 Hom.: 18966 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.467 AC: 71063 AN: 152022 Hom.: 18972 Cov.: 32 AF XY: 0.476 AC XY: 35375 AN XY: 74294

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.482

Alfa AF: 0.531 Hom.: 44227

Bravo AF: 0.460

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.3
DANN	Benign	0.75

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: rs7631734; hg19: chr3-137970907;