NM_001190787.3:c.234C>T

Variant names:

• chr5-55226651-G-A
• rs756870581
• NM_001190787.3:c.234C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001190787.3(MCIDAS):​c.234C>T​(p.Asp78Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,529,130 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (2 hom.)
• Consequence: MCIDAS NM_001190787.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.12
• Publications: 0 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

LOC124900978 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 5-55226651-G-A is Benign according to our data. Variant chr5-55226651-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 238619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00021 (32/152340) while in subpopulation AMR AF = 0.000327 (5/15308). AF 95% confidence interval is 0.000129. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD gene

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.234C>T	p.Asp78Asp	synonymous	Exon 3 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.234C>T	p.Asp78Asp	synonymous	Exon 3 of 7	ENSP00000426359.1
	MCIDAS	ENST00000513468.5	TSL:5	n.234C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000422165.1
	MCIDAS	ENST00000515336.1	TSL:5	n.171C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000371 AC: 47 AN: 126764 AF XY: 0.000332

Gnomad AFR exome AF: 0.000167

Gnomad AMR exome AF: 0.000256

Gnomad ASJ exome AF: 0.00191

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000365

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.000267 AC: 368 AN: 1376790 Hom.: 2 Cov.: 31 AF XY: 0.000277 AC XY: 188 AN XY: 679200

African (AFR) AF: 0.000705 AC: 22 AN: 31218

American (AMR) AF: 0.000258 AC: 9 AN: 34854

Ashkenazi Jewish (ASJ) AF: 0.000845 AC: 21 AN: 24838

East Asian (EAS) AF: 0.00 AC: 0 AN: 34998

South Asian (SAS) AF: 0.000115 AC: 9 AN: 78386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33710

Middle Eastern (MID) AF: 0.0140 AC: 77 AN: 5514

European-Non Finnish (NFE) AF: 0.000181 AC: 195 AN: 1075722

Other (OTH) AF: 0.000608 AC: 35 AN: 57550

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74496

African (AFR) AF: 0.000192 AC: 8 AN: 41596

American (AMR) AF: 0.000327 AC: 5 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000521 Hom.: 0

Bravo AF: 0.000276

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs756870581; hg19: chr5-54522479; COSMIC: COSV57005018; COSMIC: COSV57005018;