rs1555069023

Variant names:

• chr11-102058885-TTT-CC
• rs1555069023
• NM_032930.3:c.198_200delTTTinsCC

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_032930.3(CFAP300):​c.198_200delTTTinsCC​(p.Phe67ProfsTer10) variant causes a frameshift, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CFAP300 NM_032930.3 frameshift, missense
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:4
• Conservation: PhyloP100: 4.93
• Publications: 2 publications found

Genes affected

CFAP300 (HGNC:28188): (cilia and flagella associated protein 300) Predicted to be located in cytoplasm and motile cilium. Implicated in primary ciliary dyskinesia 38. [provided by Alliance of Genome Resources, Apr 2022]

CFAP300 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-102058885-TTT-CC is Pathogenic according to our data. Variant chr11-102058885-TTT-CC is described in ClinVar as [Pathogenic]. Clinvar id is 549862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP300	NM_032930.3	c.198_200delTTTinsCC	p.Phe67ProfsTer10	frameshift_variant, missense_variant	Exon 3 of 7	ENST00000434758.7	NP_116319.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP300	ENST00000434758.7	c.198_200delTTTinsCC	p.Phe67ProfsTer10	frameshift_variant, missense_variant	Exon 3 of 7	2	NM_032930.3	ENSP00000414390.2
CFAP300	ENST00000534360.1	c.198_200delTTTinsCC	p.Phe67ProfsTer10	frameshift_variant, missense_variant	Exon 3 of 4	1		ENSP00000435482.1
CFAP300	ENST00000530659.1	n.435_437delTTTinsCC		non_coding_transcript_exon_variant	Exon 2 of 6	1
CFAP300	ENST00000526781.5	c.198_200delTTTinsCC	p.Phe67ProfsTer10	frameshift_variant, missense_variant	Exon 3 of 6	3		ENSP00000433074.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Pathogenic:1

Dec 11, 2023

Institute Of Molecular Biology And Genetics, Federal Almazov National Medical Research Centre

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG: PVS1, PM2, PM3, PP5 -

Ciliary dyskinesia, primary, 38 Pathogenic:1

Jul 31, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Pathogenic:1

Feb 01, 2021

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CFAP300-related disorder Pathogenic:1

Sep 19, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The CFAP300 c.198_200delinsCC variant is predicted to result in a frameshift and premature protein termination (p.Phe67Profs*10). This variant has been reported in the homozygous state in two presumably unrelated patients with primary ciliary dyskinesia (previously known as C11orf70, Höben et al. 2018. PubMed ID: 29727693). This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in CFAP300 are expected to be pathogenic. This variant is interpreted as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9
Mutation Taster		=1/199	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs1555069023; hg19: chr11-101929616;