rs181843638

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001190787.3(MCIDAS):c.821G>A(p.Gly274Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,536,024 control chromosomes in the GnomAD database, including 10 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00054 ( 9 hom. )

Consequence

MCIDAS
NM_001190787.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.25

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055426955).

BP6

Variant 5-55220703-C-T is Benign according to our data. Variant chr5-55220703-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 238622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00125 (190/152368) while in subpopulation AMR AF= 0.00797 (122/15312). AF 95% confidence interval is 0.00682. There are 1 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCIDAS	NM_001190787.3 link	c.821G>A	p.Gly274Glu	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.821G>A	p.Gly274Glu	missense_variant	Exon 7 of 7	1	NM_001190787.3	ENSP00000426359.1	D6RGH6
MCIDAS	ENST00000513468.5 link	n.*285G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000422165.1	I6L8E2
MCIDAS	ENST00000513468.5 link	n.*285G>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000422165.1	I6L8E2

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

191

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00804

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00386

AC:

519

AN:

134590

Hom.:

AF XY:

0.00271

AC XY:

199

AN XY:

73304

show subpopulations

Gnomad AFR exome

AF:

0.00140

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000286

Gnomad SAS exome

AF:

0.000311

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.0000378

Gnomad OTH exome

AF:

0.00169

GnomAD4 exome

AF:

0.000536

AC:

741

AN:

1383656

Hom.:

Cov.:

AF XY:

0.000451

AC XY:

308

AN XY:

682756

show subpopulations

Gnomad4 AFR exome

AF:

0.000285

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000308

Gnomad4 SAS exome

AF:

0.000328

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.0000454

Gnomad4 OTH exome

AF:

0.000484

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152368

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.00205

ExAC

AF:

0.000169

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Aug 23, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Primary ciliary dyskinesia

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ciliary dyskinesia, primary, 42

Benign:1

Mar 09, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.70

M_CAP

Benign

0.021

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.88

REVEL

Benign

0.28

Sift

Uncertain

0.0070

Sift4G

Benign

0.22

Polyphen

0.66

Vest4

0.091

MVP

0.15

ClinPred

0.016

GERP RS

4.7

Varity_R

0.16

gMVP

0.20

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