Genetic Variant ARMC8:c.1217+55T>G (chr3-138263876-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.193

Publications

7 publications found

Variant links:

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]

ARMC8 links:

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]

NME9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC8	NM_001363941.2 link	c.1217+55T>G		intron_variant	Intron 13 of 21	ENST00000469044.6	NP_001350870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC8	ENST00000469044.6 link	c.1217+55T>G		intron_variant	Intron 13 of 21	5	NM_001363941.2	ENSP00000419413.1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75956

AN:

151892

Hom.:

21565

Cov.:

show subpopulations

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.:

AF XY:

0.600

AC XY:

400548

AN XY:

667738

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

16053

32106

48158

64211

80264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15532

31064

46596

62128

77660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.500

AC:

75988

AN:

152010

Hom.:

21572

Cov.:

AF XY:

0.509

AC XY:

37786

AN XY:

74298

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1713

3425

5138

6850

8563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over