Genetic Variant MCIDAS:p.Arg381His (chr5-55220382-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_001190787.3(MCIDAS):c.1142G>A(p.Arg381His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R381L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MCIDAS
NM_001190787.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 6.25

Publications

2 publications found

Variant links:

Genes affected

MCIDAS (HGNC:40050): (multiciliate differentiation and DNA synthesis associated cell cycle protein) This gene encodes a member of the geminin family of proteins. The encoded nuclear protein is required for the generation of multiciliated cells in respiratory epithelium. Mutations in this gene cause a rare mucociliary clearance disorder associated with recurring respiratory infections in human patients, known as reduced generation of multiple motile cilia (RGMC). [provided by RefSeq, Sep 2016]

MCIDAS Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 42
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MCIDAS links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.86

PP5

Variant 5-55220382-C-T is Pathogenic according to our data. Variant chr5-55220382-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 209009.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190787.3. 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
	MCIDAS	NM_001190787.3	MANE Select	c.1142G>A	p.Arg381His	missense	Exon 7 of 7	NP_001177716.1	D6RGH6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MCIDAS	ENST00000513312.3	TSL:1 MANE Select	c.1142G>A	p.Arg381His	missense	Exon 7 of 7	ENSP00000426359.1	D6RGH6
MCIDAS	ENST00000513468.5	TSL:5	n.*606G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000422165.1	I6L8E2
MCIDAS	ENST00000513468.5	TSL:5	n.*606G>A		3_prime_UTR	Exon 7 of 7	ENSP00000422165.1	I6L8E2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1382570

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682002

African (AFR)

AF:

0.00

AC:

AN:

31564

American (AMR)

AF:

0.00

AC:

AN:

35674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25130

East Asian (EAS)

AF:

0.00

AC:

AN:

35714

South Asian (SAS)

AF:

0.00

AC:

AN:

79152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078008

Other (OTH)

AF:

0.00

AC:

AN:

57844

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ciliary dyskinesia, primary, 42 (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.54

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.1

PhyloP100

6.3

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

REVEL

Benign

0.22

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.91

MutPred

0.45

Loss of MoRF binding (P = 5e-04)

MVP

0.17

ClinPred

0.99

GERP RS

4.9

Varity_R

0.23

gMVP

0.59

Mutation Taster

=16/84

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over