chr5-55220358-A-G

Variant names:

• chr5-55220358-A-G
• rs117929787
• NM_001190787.3:c.*8T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCIDAS	NM_001190787.3	MANE Select	c.*8T>C		3_prime_UTR	Exon 7 of 7	NP_001177716.1	D6RGH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCIDAS	ENST00000513312.3	TSL:1 MANE Select	c.*8T>C		3_prime_UTR	Exon 7 of 7	ENSP00000426359.1	D6RGH6
	MCIDAS	ENST00000513468.5	TSL:5	n.*630T>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000422165.1	I6L8E2
	MCIDAS	ENST00000513468.5	TSL:5	n.*630T>C		3_prime_UTR	Exon 7 of 7	ENSP00000422165.1	I6L8E2

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

GnomAD2 exomes AF: 0.0115 AC: 1519 AN: 132050 AF XY: 0.0115

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 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

African (AFR) AF: 0.00105 AC: 33 AN: 31480

American (AMR) AF: 0.00295 AC: 105 AN: 35546

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 420 AN: 24868

East Asian (EAS) AF: 0.0526 AC: 1873 AN: 35610

South Asian (SAS) AF: 0.00401 AC: 316 AN: 78764

European-Finnish (FIN) AF: 0.00999 AC: 337 AN: 33734

Middle Eastern (MID) AF: 0.00235 AC: 13 AN: 5538

European-Non Finnish (NFE) AF: 0.00819 AC: 8797 AN: 1074218

Other (OTH) AF: 0.0111 AC: 641 AN: 57596

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

African (AFR) AF: 0.00161 AC: 67 AN: 41582

American (AMR) AF: 0.00562 AC: 86 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.0653 AC: 338 AN: 5176

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4822

European-Finnish (FIN) AF: 0.00791 AC: 84 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00911 AC: 620 AN: 68020

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00895 Hom.: 2

Bravo AF: 0.00834

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.76
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs117929787; hg19: chr5-54516186;