Variant rs754773453 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_032930.3(CFAP300):c.433A>T(p.Arg145Ter) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.00000691 in 1,448,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CFAP300
NM_032930.3 stop_gained, splice_region

Scores

Splicing: ADA: 0.9392

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 5.42

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 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 11-102066649-A-T is Pathogenic according to our data. Variant chr11-102066649-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 549861.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-102066649-A-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFAP300	NM_032930.3 linkuse as main transcript	c.433A>T	p.Arg145Ter	stop_gained, splice_region_variant	4/7	ENST00000434758.7	NP_116319.2
CFAP300	NM_001363505.2 linkuse as main transcript	c.433A>T	p.Arg145Ter	stop_gained, splice_region_variant	4/6		NP_001350434.1
CFAP300	XM_005271713.5 linkuse as main transcript	c.433A>T	p.Arg145Ter	stop_gained, splice_region_variant	4/6		XP_005271770.1
CFAP300	NM_001195005.2 linkuse as main transcript	c.268+7694A>T		intron_variant			NP_001181934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP300	ENST00000434758.7 linkuse as main transcript	c.433A>T	p.Arg145Ter	stop_gained, splice_region_variant	4/7	2	NM_032930.3	ENSP00000414390	P1	Q9BRQ4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

238508

Hom.:

AF XY:

0.0000311

AC XY:

AN XY:

128788

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000362

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.00000691

AC:

AN:

1448210

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000902

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ciliary dyskinesia, primary, 38

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 30, 2018

- -

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

This sequence change creates a premature translational stop signal (p.Arg145*) in the C11orf70 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in C11orf70 are known to be pathogenic (PMID: 29727692, 29727693). This variant is present in population databases (rs754773453, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 29727693). ClinVar contains an entry for this variant (Variation ID: 549861). For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Uncertain

0.97

MutationTaster

Benign

1.0

A;A;D

Vest4

0.27

ClinPred

1.0

GERP RS

5.5

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.94

dbscSNV1_RF

Benign

0.56

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over