5-55220230-A-T

Position:

• chr5-55220230-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001190787.3(MCIDAS):​c.*136T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 810,086 control chromosomes in the GnomAD database, including 6,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1401 hom., cov: 33)
  • Exomes 𝑓: 0.12 (5225 hom.)
• Consequence: MCIDAS NM_001190787.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.268

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-55220230-A-T is Benign according to our data. Variant chr5-55220230-A-T is described in ClinVar as [Benign]. Clinvar id is 1222048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCIDAS	NM_001190787.3	c.*136T>A		3_prime_UTR_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.*136T>A		3_prime_UTR_variant	7/7	1	NM_001190787.3	ENSP00000426359	P1
MCIDAS	ENST00000513468.5	c.*758T>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000422165

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19783 AN: 152032 Hom.: 1397 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.119 AC: 78416 AN: 657936 Hom.: 5225 Cov.: 9 AF XY: 0.117 AC XY: 39314 AN XY: 334594

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0671

Gnomad4 ASJ exome AF: 0.0989

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.0915

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.130 AC: 19795 AN: 152150 Hom.: 1401 Cov.: 33 AF XY: 0.130 AC XY: 9688 AN XY: 74392

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.0964

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0651 Hom.: 73

Bravo AF: 0.128

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.49

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: rs463351; hg19: chr5-54516058;