5-55220448-C-T

Variant names:

• chr5-55220448-C-T
• NM_001190787.3:c.1076G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001190787.3(MCIDAS):​c.1076G>A​(p.Arg359His) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MCIDAS NM_001190787.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCIDAS	NM_001190787.3	c.1076G>A	p.Arg359His	missense_variant	Exon 7 of 7	ENST00000513312.3	NP_001177716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCIDAS	ENST00000513312.3	c.1076G>A	p.Arg359His	missense_variant	Exon 7 of 7	1	NM_001190787.3	ENSP00000426359.1
MCIDAS	ENST00000513468.5	n.*540G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000422165.1
MCIDAS	ENST00000513468.5	n.*540G>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000422165.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383790 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 682840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.49		Loss of MoRF binding (P = 0.0329);
MVP		0.13
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.22
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-54516276; COSMIC: COSV101563746; COSMIC: COSV101563746;