Variant chr5-55220488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001190787.3(MCIDAS):c.1036G>A(p.Gly346Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MCIDAS
NM_001190787.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07527843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCIDAS	NM_001190787.3 linkuse as main transcript	c.1036G>A	p.Gly346Ser	missense_variant	7/7	ENST00000513312.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCIDAS	ENST00000513312.3 linkuse as main transcript	c.1036G>A	p.Gly346Ser	missense_variant	7/7	1	NM_001190787.3	P1
MCIDAS	ENST00000513468.5 linkuse as main transcript	c.*500G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1383730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2024

The c.1036G>A (p.G346S) alteration is located in exon 7 (coding exon 7) of the MCIDAS gene. This alteration results from a G to A substitution at nucleotide position 1036, causing the glycine (G) at amino acid position 346 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.72

M_CAP

Benign

0.0035

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.93

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.76

REVEL

Benign

0.15

Sift

Benign

0.71

Sift4G

Benign

0.59

Polyphen

0.046

Vest4

0.32

MutPred

0.21

Gain of glycosylation at G346 (P = 0.0197);

MVP

0.055

ClinPred

0.56

GERP RS

3.9

Varity_R

0.061

gMVP

0.52

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