rs186341559

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4BP6BS1BS2

The NM_001190787.3(MCIDAS):c.120+3G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0045 in 1,520,420 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 31 hom. )

Consequence

MCIDAS
NM_001190787.3 splice_region, intron

Scores

Splicing: ADA: 0.07003

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 4.30

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 links:

LOC124900978 (HGNC:):

LOC124900978 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.17).

BP6

Variant 5-55227016-C-T is Benign according to our data. Variant chr5-55227016-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 238618.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=2}.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00349 (532/152328) while in subpopulation SAS AF = 0.00601 (29/4828). AF 95% confidence interval is 0.00448. There are 5 homozygotes in GnomAd4. There are 256 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCIDAS	NM_001190787.3 link	c.120+3G>A		splice_region_variant, intron_variant	Intron 1 of 6	ENST00000513312.3	NP_001177716.1	D6RGH6
LOC124900978	XR_007058773.1 link	n.399C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCIDAS	ENST00000513312.3 link	c.120+3G>A	splice_region_variant, intron_variant	Intron 1 of 6	1	NM_001190787.3	ENSP00000426359.1	D6RGH6
MCIDAS	ENST00000513468.5 link	n.120+3G>A	splice_region_variant, intron_variant	Intron 1 of 6	5		ENSP00000422165.1	I6L8E2
MCIDAS	ENST00000515336.1 link	n.58-85G>A	intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

534

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.00492

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00501

AC:

563

AN:

112322

AF XY:

0.00521

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.00564

Gnomad ASJ exome

AF:

0.00426

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00508

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00461

AC:

6309

AN:

1368092

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

3259

AN XY:

675090

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

AC:

AN:

28964

Gnomad4 AMR exome

AF:

0.00632

AC:

219

AN:

34674

Gnomad4 ASJ exome

AF:

0.00366

AC:

AN:

24586

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

32874

Gnomad4 SAS exome

AF:

0.00752

AC:

589

AN:

78352

Gnomad4 FIN exome

AF:

0.00135

AC:

AN:

33290

Gnomad4 NFE exome

AF:

0.00449

AC:

4817

AN:

1072458

Gnomad4 Remaining exome

AF:

0.00595

AC:

341

AN:

57264

Heterozygous variant carriers

378

755

1133

1510

1888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.00349

AC:

532

AN:

152328

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

256

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00101

AC:

0.00100996

AN:

0.00100996

Gnomad4 AMR

AF:

0.00340

AC:

0.00339647

AN:

0.00339647

Gnomad4 ASJ

AF:

0.00346

AC:

0.00345821

AN:

0.00345821

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00601

AC:

0.00600663

AN:

0.00600663

Gnomad4 FIN

AF:

0.00113

AC:

0.00113016

AN:

0.00113016

Gnomad4 NFE

AF:

0.00491

AC:

0.0049096

AN:

0.0049096

Gnomad4 OTH

AF:

0.00710

AC:

0.00710227

AN:

0.00710227

Heterozygous variant carriers

118

147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

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:

0.00417

Hom.:

Bravo

AF:

0.00357

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MCIDAS: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Ciliary dyskinesia, primary, 42

Uncertain:1

Feb 18, 2020

Genetics and Molecular Pathology, SA Pathology

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.98

Mutation Taster

=39/61

disease causing

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.070

dbscSNV1_RF

Benign

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over