chr5-55220439-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001190787.3(MCIDAS):c.1085C>T(p.Ala362Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000846 in 1,536,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MCIDAS
NM_001190787.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 4.88

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017221868).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000453 (69/152278) while in subpopulation AFR AF = 0.00164 (68/41556). AF 95% confidence interval is 0.00132. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.1085C>T	p.Ala362Val	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.1085C>T	p.Ala362Val	missense	Exon 7 of 7	ENSP00000426359.1	D6RGH6
MCIDAS	ENST00000513468.5	TSL:5	n.*549C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000422165.1	I6L8E2
MCIDAS	ENST00000513468.5	TSL:5	n.*549C>T		3_prime_UTR	Exon 7 of 7	ENSP00000422165.1	I6L8E2

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000741

AC:

AN:

134922

AF XY:

0.0000681

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000441

AC:

AN:

1383802

Hom.:

Cov.:

AF XY:

0.0000381

AC XY:

AN XY:

682842

show subpopulations

African (AFR)

AF:

0.00177

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00000371

AC:

AN:

1078882

Other (OTH)

AF:

0.0000173

AC:

AN:

57902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000453

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41556

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000641

Hom.:

Bravo

AF:

0.000472

ExAC

AF:

0.0000949

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.77

M_CAP

Benign

0.018

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.1

PhyloP100

4.9

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.0

REVEL

Benign

0.11

Sift

Benign

0.16

Sift4G

Pathogenic

0.0

Polyphen

0.47

Vest4

0.17

MutPred

0.32

Gain of sheet (P = 0.0101)

MVP

0.099

ClinPred

0.12

GERP RS

4.8

Varity_R

0.19

gMVP

0.58

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over