5-55220358-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001190787.3(MCIDAS):c.*8T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00905 in 1,529,672 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (99 hom.)
• Consequence: MCIDAS NM_001190787.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.538

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-55220358-A-G is Benign according to our data. Variant chr5-55220358-A-G is described in ClinVar as [Benign]. Clinvar id is 1287962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCIDAS	NM_001190787.3	c.*8T>C		3_prime_UTR_variant	7/7	ENST00000513312.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCIDAS	ENST00000513312.3	c.*8T>C		3_prime_UTR_variant	7/7	1	NM_001190787.3	P1
MCIDAS	ENST00000513468.5	c.*630T>C		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes AF: 0.00862 AC: 1312 AN: 152200 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00791

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00911

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0115 AC: 1519 AN: 132050 Hom.: 24 AF XY: 0.0115 AC XY: 823 AN XY: 71736

Gnomad AFR exome AF: 0.00140

Gnomad AMR exome AF: 0.00300

Gnomad ASJ exome AF: 0.0176

Gnomad EAS exome AF: 0.0641

Gnomad SAS exome AF: 0.00431

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.00857

Gnomad OTH exome AF: 0.00786

GnomAD4 exome AF: 0.00910 AC: 12535 AN: 1377354 Hom.: 99 Cov.: 30 AF XY: 0.00906 AC XY: 6145 AN XY: 678504

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.0526

Gnomad4 SAS exome AF: 0.00401

Gnomad4 FIN exome AF: 0.00999

Gnomad4 NFE exome AF: 0.00819

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.00861 AC: 1311 AN: 152318 Hom.: 18 Cov.: 33 AF XY: 0.00865 AC XY: 644 AN XY: 74478

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0653

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00791

Gnomad4 NFE AF: 0.00911

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00938 Hom.: 2

Bravo AF: 0.00834

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.5
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs117929787; hg19: chr5-54516186;