chr5-55222308-C-T

Variant names:

• chr5-55222308-C-T
• rs1001897568
• NM_001190787.3:c.474G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_001190787.3(MCIDAS):​c.474G>A​(p.Pro158Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000593 in 1,535,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: MCIDAS NM_001190787.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -2.30
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-55222308-C-T is Benign according to our data. Variant chr5-55222308-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 454530.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000112 (17/152068) while in subpopulation NFE AF = 0.000176 (12/68004). AF 95% confidence interval is 0.000102. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.474G>A	p.Pro158Pro	synonymous	Exon 5 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.474G>A	p.Pro158Pro	synonymous	Exon 5 of 7	ENSP00000426359.1
	MCIDAS	ENST00000513468.5	TSL:5	n.478G>A		non_coding_transcript_exon	Exon 5 of 7	ENSP00000422165.1
	MCIDAS	ENST00000515336.1	TSL:5	n.411G>A		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000447 AC: 6 AN: 134082 AF XY: 0.0000411

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000570

Gnomad OTH exome AF: 0.000485

GnomAD4 exome AF: 0.0000535 AC: 74 AN: 1383256 Hom.: 0 Cov.: 31 AF XY: 0.0000498 AC XY: 34 AN XY: 682540

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.0000841 AC: 3 AN: 35654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35700

South Asian (SAS) AF: 0.00 AC: 0 AN: 79190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.0000612 AC: 66 AN: 1078540

Other (OTH) AF: 0.0000864 AC: 5 AN: 57888

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74272

African (AFR) AF: 0.0000483 AC: 2 AN: 41398

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000144

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MCIDAS-related disorder (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1001897568; hg19: chr5-54518136;