rs199825346

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001190787.3(MCIDAS):c.739C>T(p.Arg247Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,530,240 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0058 ( 34 hom. )

Consequence

MCIDAS
NM_001190787.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.0300

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00433442).

BP6

Variant 5-55220785-G-A is Benign according to our data. Variant chr5-55220785-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 238621.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00374 (569/152304) while in subpopulation NFE AF= 0.00653 (444/68028). AF 95% confidence interval is 0.00603. There are 2 homozygotes in gnomad4. There are 266 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCIDAS	NM_001190787.3 link	c.739C>T	p.Arg247Trp	missense_variant	Exon 7 of 7	ENST00000513312.3	NP_001177716.1	D6RGH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCIDAS	ENST00000513312.3 link	c.739C>T	p.Arg247Trp	missense_variant	Exon 7 of 7	1	NM_001190787.3	ENSP00000426359.1	D6RGH6
MCIDAS	ENST00000513468.5 link	n.*203C>T		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000422165.1	I6L8E2
MCIDAS	ENST00000513468.5 link	n.*203C>T		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000422165.1	I6L8E2

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

568

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00651

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00332

AC:

446

AN:

134210

Hom.:

AF XY:

0.00322

AC XY:

235

AN XY:

73076

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000936

Gnomad FIN exome

AF:

0.000942

Gnomad NFE exome

AF:

0.00578

Gnomad OTH exome

AF:

0.00484

GnomAD4 exome

AF:

0.00580

AC:

7994

AN:

1377936

Hom.:

Cov.:

AF XY:

0.00566

AC XY:

3842

AN XY:

678628

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00365

Gnomad4 ASJ exome

AF:

0.0000797

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000872

Gnomad4 FIN exome

AF:

0.000769

Gnomad4 NFE exome

AF:

0.00699

Gnomad4 OTH exome

AF:

0.00393

GnomAD4 genome

AF:

0.00374

AC:

569

AN:

152304

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00653

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00223

Hom.:

Bravo

AF:

0.00386

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00856

AC:

ExAC

AF:

0.00139

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 10, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ciliary dyskinesia, primary, 42

Benign:1

Jan 03, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.022

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Benign

0.060

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.18

MVP

0.25

ClinPred

0.032

GERP RS

2.0

Varity_R

0.074

gMVP

0.29

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

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