5-55220693-G-C

Position:

• chr5-55220693-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001190787.3(MCIDAS):​c.831C>G​(p.Cys277Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCIDAS NM_001190787.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26453084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCIDAS	NM_001190787.3	c.831C>G	p.Cys277Trp	missense_variant	7/7	ENST00000513312.3	NP_001177716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCIDAS	ENST00000513312.3	c.831C>G	p.Cys277Trp	missense_variant	7/7	1	NM_001190787.3	ENSP00000426359	P1
MCIDAS	ENST00000513468.5	c.*295C>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000422165

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	0.069
Eigen_PC	Benign	0.0080
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.032	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.43		Loss of disorder (P = 0.0449);
MVP		0.37
ClinPred		0.80	D
GERP RS		1.7
Varity_R		0.46
gMVP		0.50

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: rs6879219; hg19: chr5-54516521;