rs190259474

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001190787.3(MCIDAS):c.162G>T(p.Gly54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,415,894 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

MCIDAS
NM_001190787.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.556

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 5-55226890-C-A is Benign according to our data. Variant chr5-55226890-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 454526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.556 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00088 (134/152340) while in subpopulation AMR AF= 0.0066 (101/15312). AF 95% confidence interval is 0.00555. There are 0 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCIDAS	NM_001190787.3 linkuse as main transcript	c.162G>T	p.Gly54=	synonymous_variant	2/7	ENST00000513312.3
LOC124900978	XR_007058773.1 linkuse as main transcript	n.273C>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MCIDAS	ENST00000513312.3 linkuse as main transcript	c.162G>T	p.Gly54=	synonymous_variant	2/7	1	NM_001190787.3	P1
MCIDAS	ENST00000515336.1 linkuse as main transcript	n.99G>T		non_coding_transcript_exon_variant	2/6	5
MCIDAS	ENST00000513468.5 linkuse as main transcript	c.162G>T	p.Gly54=	synonymous_variant, NMD_transcript_variant	2/7	5

Frequencies

GnomAD3 genomes

AF:

0.000880

AC:

134

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00660

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00201

AC:

AN:

27918

Hom.:

AF XY:

0.00164

AC XY:

AN XY:

15214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000566

Gnomad OTH exome

AF:

0.00220

GnomAD4 exome

AF:

0.000379

AC:

479

AN:

1263554

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

220

AN XY:

614006

show subpopulations

Gnomad4 AFR exome

AF:

0.000200

Gnomad4 AMR exome

AF:

0.00617

Gnomad4 ASJ exome

AF:

0.000537

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000296

Gnomad4 OTH exome

AF:

0.000801

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152340

Hom.:

Cov.:

AF XY:

0.000805

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000520

Hom.:

Bravo

AF:

0.00145

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 13, 2024

- -

Ciliary dyskinesia, primary, 42

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

Cadd

Benign

7.5

Dann

Benign

0.74

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

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