Variant rs746633371 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004928.3(CFAP410):c.436_466delGAGAGAGAGGGCACAGGCCACGGCGGCCCCA(p.Glu146fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CFAP410
NM_004928.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

CFAP410 (HGNC:1260): (cilia and flagella associated protein 410) Four alternatively spliced transcript variants encoding four different isoforms have been found for this nuclear gene. All isoforms contain leucine-rich repeats. Three of these isoforms are mitochondrial proteins and one of them lacks the target peptide, so is not located in mitochondrion. This gene is down-regulated in Down syndrome (DS) brain, which may represent mitochondrial dysfunction in DS patients. [provided by RefSeq, Sep 2012]

CFAP410 links:

CFAP410 (HGNC:):

CFAP410 links:

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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 21-44331921-TTGGGGCCGCCGTGGCCTGTGCCCTCTCTCTC-T is Pathogenic according to our data. Variant chr21-44331921-TTGGGGCCGCCGTGGCCTGTGCCCTCTCTCTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 428576.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-44331921-TTGGGGCCGCCGTGGCCTGTGCCCTCTCTCTC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP410	NM_004928.3 linkuse as main transcript	c.436_466delGAGAGAGAGGGCACAGGCCACGGCGGCCCCA	p.Glu146fs	frameshift_variant	5/7	ENST00000339818.9	NP_004919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP410	ENST00000339818.9 linkuse as main transcript	c.436_466delGAGAGAGAGGGCACAGGCCACGGCGGCCCCA	p.Glu146fs	frameshift_variant	5/7	1	NM_004928.3	ENSP00000344566.4		O43822-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249120

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135094

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461090

Hom.:

AF XY:

0.00000275

AC XY:

AN XY:

726848

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2023

ClinVar contains an entry for this variant (Variation ID: 428576). This sequence change creates a premature translational stop signal (p.Glu146Serfs*6) in the CFAP410 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFAP410 are known to be pathogenic (PMID: 23105016, 26167768). This variant is present in population databases (rs746633371, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with inherited retinal dystrophy (PMID: 26294103). For these reasons, this variant has been classified as Pathogenic. -

Retinal dystrophy with or without macular staphyloma

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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