Menu
GeneBe

rs375687696

chr5-55220462-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001190787.3(MCIDAS):c.1062C>T(p.Ser354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,536,076 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 21 hom. )

Consequence

MCIDAS
NM_001190787.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0820
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-55220462-G-A is Benign according to our data. Variant chr5-55220462-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 238617.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.082 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00141 (215/152296) while in subpopulation SAS AF= 0.00994 (48/4828). AF 95% confidence interval is 0.0077. There are 1 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MCIDASNM_001190787.3 linkuse as main transcriptc.1062C>T p.Ser354= synonymous_variant 7/7 ENST00000513312.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCIDASENST00000513312.3 linkuse as main transcriptc.1062C>T p.Ser354= synonymous_variant 7/71 NM_001190787.3 P1
MCIDASENST00000513468.5 linkuse as main transcriptc.*526C>T 3_prime_UTR_variant, NMD_transcript_variant 7/75

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00141
AC:
215
AN:
152178
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00993
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00165
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.00296
AC:
399
AN:
134914
Hom.:
6
AF XY:
0.00353
AC XY:
259
AN XY:
73380
show subpopulations
Gnomad AFR exome
AF:
0.000459
Gnomad AMR exome
AF:
0.00102
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000951
Gnomad SAS exome
AF:
0.0122
Gnomad FIN exome
AF:
0.000557
Gnomad NFE exome
AF:
0.00158
Gnomad OTH exome
AF:
0.00192
GnomAD4 exome
AF:
0.00218
AC:
3021
AN:
1383780
Hom.:
21
Cov.:
30
AF XY:
0.00255
AC XY:
1739
AN XY:
682828
show subpopulations
Gnomad4 AFR exome
AF:
0.000253
Gnomad4 AMR exome
AF:
0.000896
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0123
Gnomad4 FIN exome
AF:
0.000354
Gnomad4 NFE exome
AF:
0.00172
Gnomad4 OTH exome
AF:
0.00197
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00141
AC:
215
AN:
152296
Hom.:
1
Cov.:
33
AF XY:
0.00156
AC XY:
116
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00994
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00165
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.00108
Hom.:
0
Bravo
AF:
0.000990
Asia WGS
AF:
0.00664
AC:
23
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 15, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
13
Dann
Benign
0.90

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.

Other links and lift over

dbSNP: rs375687696; hg19: chr5-54516290; API