Genetic Variant CFAP54:p.Phe1571LeufsTer4 (chr12-96649909-CATTT-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001306084.2(CFAP54):c.4713_4716delTATT(p.Phe1571LeufsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,595,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CFAP54
NM_001306084.2 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

CFAP54 (HGNC:26456): (cilia and flagella associated protein 54) Predicted to be involved in cilium assembly; cilium movement involved in cell motility; and spermatogenesis. Predicted to act upstream of or within cerebrospinal fluid circulation; motile cilium assembly; and mucociliary clearance. Predicted to be located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CFAP54 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 12-96649909-CATTT-C is Pathogenic according to our data. Variant chr12-96649909-CATTT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3778415.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP54	NM_001306084.2 link	c.4713_4716delTATT	p.Phe1571LeufsTer4	frameshift_variant	Exon 35 of 68	ENST00000524981.9	NP_001293013.1	Q96N23-1
CFAP54	NM_001367885.1 link	c.4713_4716delTATT	p.Phe1571LeufsTer4	frameshift_variant	Exon 35 of 69		NP_001354814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP54	ENST00000524981.9 link	c.4713_4716delTATT	p.Phe1571LeufsTer4	frameshift_variant	Exon 35 of 68	5	NM_001306084.2	ENSP00000431759.5	Q96N23-1
CFAP54	ENST00000637336.1 link	c.1428_1431delTATT	p.Phe476fs	frameshift_variant	Exon 12 of 46	5		ENSP00000490000.1	A0A1B0GU80
CFAP54	ENST00000342887.1 link	n.66_69delTATT		non_coding_transcript_exon_variant	Exon 2 of 27	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443552

Hom.:

AF XY:

0.00

AC XY:

AN XY:

718142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CFAP54: PVS1:Strong, PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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