NM_001105247.2:c.1643T>C

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001105247.2(ARMC5):c.1643T>C(p.Leu548Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ARMC5
NM_001105247.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.62

Publications

4 publications found

Variant links:

Genes affected

ARMC5 (HGNC:25781): (armadillo repeat containing 5) This gene encodes a member of the ARM (armadillo/beta-catenin-like repeat) superfamily. The ARM repeat is a tandemly repeated sequence motif with approximately 40 amino acid long. This repeat is implicated in mediating protein-protein interactions. The encoded protein contains seven ARM repeats. Mutations in this gene are associated with primary bilateral macronodular adrenal hyperplasia, which is also known as ACTH-independent macronodular adrenal hyperplasia 2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ARMC5 Gene-Disease associations (from GenCC):

ACTH-independent macronodular adrenal hyperplasia 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
Cushing syndrome due to macronodular adrenal hyperplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ARMC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.941

PP5

Variant 16-31464666-T-C is Pathogenic according to our data. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31464666-T-C is described in CliVar as Pathogenic. Clinvar id is 144055.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC5	NM_001105247.2 link	c.1643T>C	p.Leu548Pro	missense_variant	Exon 4 of 6	ENST00000268314.9	NP_001098717.1	Q96C12-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC5	ENST00000268314.9 link	c.1643T>C	p.Leu548Pro	missense_variant	Exon 4 of 6	5	NM_001105247.2	ENSP00000268314.4		Q96C12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446392

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110922

Other (OTH)

AF:

0.00

AC:

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ACTH-independent macronodular adrenal hyperplasia 2

Pathogenic:1

Nov 28, 2013

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;T;T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.69

T;T;.;T;T

M_CAP

Pathogenic

0.71

MetaRNN

Pathogenic

0.94

D;D;D;D;D

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.1

.;M;M;M;.

PhyloP100

2.6

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.4

D;D;D;D;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.0030

D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

.;D;D;D;.

Vest4

0.94

MVP

0.61

MPC

1.9

ClinPred

0.95

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.79

gMVP

0.87

Mutation Taster

=2/98

disease causing (ClinVar)

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over