rs463351

Variant names:

• chr5-55220230-A-T
• rs463351
• NM_001190787.3:c.*136T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-55220230-A-T
• chr5-55220230-A-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 VariationId 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.

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.*136T>A		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.*136T>A		3_prime_UTR	Exon 7 of 7	ENSP00000426359.1	D6RGH6
	MCIDAS	ENST00000513468.5	TSL:5	n.*758T>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000422165.1	I6L8E2
	MCIDAS	ENST00000513468.5	TSL:5	n.*758T>A		3_prime_UTR	Exon 7 of 7	ENSP00000422165.1	I6L8E2

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

African (AFR) AF: 0.158 AC: 2566 AN: 16288

American (AMR) AF: 0.0671 AC: 1273 AN: 18980

Ashkenazi Jewish (ASJ) AF: 0.0989 AC: 1483 AN: 14998

East Asian (EAS) AF: 0.261 AC: 8338 AN: 31952

South Asian (SAS) AF: 0.0915 AC: 4470 AN: 48834

European-Finnish (FIN) AF: 0.140 AC: 4146 AN: 29710

Middle Eastern (MID) AF: 0.136 AC: 337 AN: 2476

European-Non Finnish (NFE) AF: 0.112 AC: 51840 AN: 461754

Other (OTH) AF: 0.120 AC: 3963 AN: 32944

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

African (AFR) AF: 0.158 AC: 6569 AN: 41498

American (AMR) AF: 0.0835 AC: 1277 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1379 AN: 5174

South Asian (SAS) AF: 0.0964 AC: 465 AN: 4826

European-Finnish (FIN) AF: 0.132 AC: 1400 AN: 10580

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7968 AN: 67996

Other (OTH) AF: 0.118 AC: 249 AN: 2114

Alfa AF: 0.0651 Hom.: 73

Bravo AF: 0.128

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.49
PhyloP100		-0.27
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: rs463351; hg19: chr5-54516058;