Genetic Variant CFAP54:p.Arg293His (chr12-96519007-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001306084.2(CFAP54):c.878G>A(p.Arg293His) variant causes a missense change. The variant allele was found at a frequency of 0.0000938 in 1,535,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

CFAP54
NM_001306084.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.51

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 12-96519007-G-A is Pathogenic according to our data. Variant chr12-96519007-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3767881.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.3960695). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP54	NM_001306084.2 link	c.878G>A	p.Arg293His	missense_variant	Exon 6 of 68	ENST00000524981.9	NP_001293013.1	Q96N23-1
CFAP54	NM_001367885.1 link	c.878G>A	p.Arg293His	missense_variant	Exon 6 of 69		NP_001354814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP54	ENST00000524981.9 link	c.878G>A	p.Arg293His	missense_variant	Exon 6 of 68	5	NM_001306084.2	ENSP00000431759.5		Q96N23-1
CFAP54	ENST00000553778.6 link	n.734G>A		non_coding_transcript_exon_variant	Exon 5 of 12	1		ENSP00000452066.2		A0A0A0MTQ3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

137052

Hom.:

AF XY:

0.0000134

AC XY:

AN XY:

74514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000874

AC:

121

AN:

1383760

Hom.:

Cov.:

AF XY:

0.0000718

AC XY:

AN XY:

682816

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000295

Gnomad4 NFE exome

AF:

0.0000992

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.000151

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000113

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spermatogenic failure 98

Pathogenic:1

Mar 11, 2025

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0073

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.44

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.31

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Vest4

0.46

MVP

0.085

MPC

0.29

ClinPred

0.29

GERP RS

5.4

Varity_R

0.33

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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