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GeneBe

rs372120150

chr5-55220750-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001190787.3(MCIDAS):c.774C>T(p.Leu258=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 1,534,914 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00095 ( 17 hom. )

Consequence

MCIDAS
NM_001190787.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.732
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-55220750-G-A is Benign according to our data. Variant chr5-55220750-G-A is described in ClinVar as [Benign]. Clinvar id is 454531.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=0.732 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 = 0.000427 (65/152352) while in subpopulation SAS AF= 0.013 (63/4832). AF 95% confidence interval is 0.0105. There are 0 homozygotes in gnomad4. There are 50 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.774C>T p.Leu258= synonymous_variant 7/7 ENST00000513312.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCIDASENST00000513312.3 linkuse as main transcriptc.774C>T p.Leu258= synonymous_variant 7/71 NM_001190787.3 P1
MCIDASENST00000513468.5 linkuse as main transcriptc.*238C>T 3_prime_UTR_variant, NMD_transcript_variant 7/75

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000427
AC:
65
AN:
152234
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0130
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00264
AC:
355
AN:
134568
Hom.:
6
AF XY:
0.00340
AC XY:
249
AN XY:
73286
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000409
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0153
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000568
Gnomad OTH exome
AF:
0.00145
GnomAD4 exome
AF:
0.000946
AC:
1308
AN:
1382562
Hom.:
17
Cov.:
35
AF XY:
0.00137
AC XY:
935
AN XY:
681924
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0155
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000195
Gnomad4 OTH exome
AF:
0.000934
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000427
AC:
65
AN:
152352
Hom.:
0
Cov.:
34
AF XY:
0.000671
AC XY:
50
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0130
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000256
Hom.:
0
Bravo
AF:
0.0000907
Asia WGS
AF:
0.00635
AC:
22
AN:
3478

ClinVar

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

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 17, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
5.2
Dann
Benign
0.93

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: rs372120150; hg19: chr5-54516578; API