5-55221095-T-G

Variant names:

• chr5-55221095-T-G
• rs878854270
• NM_001190787.3:c.638A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001190787.3(MCIDAS):​c.638A>C​(p.Glu213Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E213G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCIDAS NM_001190787.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.35
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 42

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35738826).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190787.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCIDAS	NM_001190787.3	MANE Select	c.638A>C	p.Glu213Ala	missense	Exon 6 of 7	NP_001177716.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCIDAS	ENST00000513312.3	TSL:1 MANE Select	c.638A>C	p.Glu213Ala	missense	Exon 6 of 7	ENSP00000426359.1
	MCIDAS	ENST00000513468.5	TSL:5	n.*102A>C		non_coding_transcript_exon	Exon 6 of 7	ENSP00000422165.1
	MCIDAS	ENST00000513468.5	TSL:5	n.*102A>C		3_prime_UTR	Exon 6 of 7	ENSP00000422165.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.23	B
Vest4		0.69
MutPred		0.17		Gain of helix (P = 0.062)
MVP		0.18
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.73
gMVP		0.75
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs878854270; hg19: chr5-54516923;