3-138263876-T-G

Variant names:

• chr3-138263876-T-G
• rs939453
• NM_001363941.2:c.1217+55T>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.1217+55T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,479,762 control chromosomes in the GnomAD database, including 264,052 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 0.50 (21572 hom., cov: 32)
  • Exomes 𝑓: 0.60 (242480 hom.)
• Consequence: ARMC8 NM_001363941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 7 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]

NME9 (HGNC:21343): (NME/NM23 family member 9) Predicted to enable nucleoside diphosphate kinase activity. Predicted to be involved in nucleotide metabolic process. Predicted to be located in dynein axonemal particle. [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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC8	NM_001363941.2	MANE Select	c.1217+55T>G		intron	N/A	NP_001350870.1	Q8IUR7-1
	ARMC8	NM_015396.6		c.1175+55T>G		intron	N/A	NP_056211.2
	ARMC8	NM_001267041.2		c.1124+55T>G		intron	N/A	NP_001253970.1	B7Z637

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC8	ENST00000469044.6	TSL:5 MANE Select	c.1217+55T>G		intron	N/A	ENSP00000419413.1	Q8IUR7-1
	ARMC8	ENST00000481646.5	TSL:1	c.1175+55T>G		intron	N/A	ENSP00000420333.1	Q8IUR7-2
	NME9	ENST00000492993.5	TSL:1	n.*66-1290A>C		intron	N/A	ENSP00000419355.1	Q3KNW3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75956 AN: 151892 Hom.: 21565 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.600 AC: 796166 AN: 1327752 Hom.: 242480 Cov.: 19 AF XY: 0.600 AC XY: 400548 AN XY: 667738

African (AFR) AF: 0.213 AC: 6464 AN: 30378

American (AMR) AF: 0.751 AC: 33437 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 14127 AN: 25290

East Asian (EAS) AF: 0.837 AC: 32715 AN: 39096

South Asian (SAS) AF: 0.621 AC: 51860 AN: 83454

European-Finnish (FIN) AF: 0.618 AC: 32916 AN: 53296

Middle Eastern (MID) AF: 0.533 AC: 2925 AN: 5484

European-Non Finnish (NFE) AF: 0.595 AC: 588887 AN: 990266

Other (OTH) AF: 0.587 AC: 32835 AN: 55936

GnomAD4 genome AF: 0.500 AC: 75988 AN: 152010 Hom.: 21572 Cov.: 32 AF XY: 0.509 AC XY: 37786 AN XY: 74298

African (AFR) AF: 0.223 AC: 9252 AN: 41460

American (AMR) AF: 0.625 AC: 9551 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4330 AN: 5166

South Asian (SAS) AF: 0.635 AC: 3061 AN: 4822

European-Finnish (FIN) AF: 0.636 AC: 6714 AN: 10550

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39489 AN: 67948

Other (OTH) AF: 0.512 AC: 1080 AN: 2110

Alfa AF: 0.543 Hom.: 5440

Bravo AF: 0.491

Asia WGS AF: 0.693 AC: 2411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.68
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs939453; hg19: chr3-137982718; COSMIC: COSV58623743;