rs771063151

Variant names:

• chr5-55226672-G-GCGGGGAGA
• rs771063151
• NM_001190787.3:c.218-13_218-6dupTCTCCCCG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001190787.3(MCIDAS):​c.218-13_218-6dupTCTCCCCG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000724 in 1,499,124 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00075 (5 hom.)
• Consequence: MCIDAS NM_001190787.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.252

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]

LOC124900978 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-55226672-G-GCGGGGAGA is Benign according to our data. Variant chr5-55226672-G-GCGGGGAGA is described in ClinVar as [Likely_benign]. Clinvar id is 454527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000492 (75/152314) while in subpopulation SAS AF= 0.00145 (7/4830). AF 95% confidence interval is 0.000679. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCIDAS	NM_001190787.3	c.218-13_218-6dupTCTCCCCG		splice_region_variant, intron_variant	Intron 2 of 6	ENST00000513312.3	NP_001177716.1
LOC124900978	XR_007058773.1	n.57_64dupGGGGAGAC		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCIDAS	ENST00000513312.3	c.218-6_218-5insTCTCCCCG		splice_region_variant, intron_variant	Intron 2 of 6	1	NM_001190787.3	ENSP00000426359.1
MCIDAS	ENST00000513468.5	n.218-6_218-5insTCTCCCCG		splice_region_variant, intron_variant	Intron 2 of 6	5		ENSP00000422165.1
MCIDAS	ENST00000515336.1	n.155-6_155-5insTCTCCCCG		splice_region_variant, intron_variant	Intron 2 of 5	5

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000357 AC: 35 AN: 97914 Hom.: 0 AF XY: 0.000389 AC XY: 21 AN XY: 53982

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000531

Gnomad FIN exome AF: 0.000237

Gnomad NFE exome AF: 0.000591

Gnomad OTH exome AF: 0.000669

GnomAD4 exome AF: 0.000750 AC: 1010 AN: 1346810 Hom.: 5 Cov.: 31 AF XY: 0.000775 AC XY: 513 AN XY: 662288

Gnomad4 AFR exome AF: 0.000102

Gnomad4 AMR exome AF: 0.0000663

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000790

Gnomad4 FIN exome AF: 0.0000906

Gnomad4 NFE exome AF: 0.000850

Gnomad4 OTH exome AF: 0.000677

GnomAD4 genome AF: 0.000492 AC: 75 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74472

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000480 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Dec 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MCIDAS-related disorder Benign:1

May 19, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Ciliary dyskinesia, primary, 42 Benign:1

Feb 24, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs771063151; hg19: chr5-54522500;