3-138211503-T-G

Variant names:

• chr3-138211503-T-G
• rs774801
• NM_001363941.2:c.122+1610T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363941.2(ARMC8):​c.122+1610T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,042 control chromosomes in the GnomAD database, including 19,140 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 (19140 hom., cov: 32)
• Consequence: ARMC8 NM_001363941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363941.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC8	NM_001363941.2	MANE Select	c.122+1610T>G		intron	N/A	NP_001350870.1
	ARMC8	NM_015396.6		c.80+1610T>G		intron	N/A	NP_056211.2
	ARMC8	NM_001267041.2		c.122+1610T>G		intron	N/A	NP_001253970.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC8	ENST00000469044.6	TSL:5 MANE Select	c.122+1610T>G		intron	N/A	ENSP00000419413.1
	ARMC8	ENST00000481646.5	TSL:1	c.80+1610T>G		intron	N/A	ENSP00000420333.1
	ARMC8	ENST00000358441.6	TSL:1	c.80+1610T>G		intron	N/A	ENSP00000351221.2

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71420 AN: 151924 Hom.: 19130 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.470 AC: 71454 AN: 152042 Hom.: 19140 Cov.: 32 AF XY: 0.479 AC XY: 35600 AN XY: 74336

African (AFR) AF: 0.212 AC: 8793 AN: 41476

American (AMR) AF: 0.596 AC: 9109 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1843 AN: 3466

East Asian (EAS) AF: 0.840 AC: 4351 AN: 5178

South Asian (SAS) AF: 0.548 AC: 2645 AN: 4828

European-Finnish (FIN) AF: 0.618 AC: 6534 AN: 10568

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36588 AN: 67936

Other (OTH) AF: 0.488 AC: 1029 AN: 2110

Alfa AF: 0.515 Hom.: 11582

Bravo AF: 0.463

Asia WGS AF: 0.658 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.71
PhyloP100		-1.1
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: rs774801; hg19: chr3-137930345;