Variant 12-96644400-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001306084.2(CFAP54):c.4539G>C(p.Met1513Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,527,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CFAP54
NM_001306084.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0520

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02189833).

BP6

Variant 12-96644400-G-C is Benign according to our data. Variant chr12-96644400-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2672516.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP54	NM_001306084.2 linkuse as main transcript	c.4539G>C	p.Met1513Ile	missense_variant	33/68	ENST00000524981.9
CFAP54	NM_001367885.1 linkuse as main transcript	c.4539G>C	p.Met1513Ile	missense_variant	33/69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP54	ENST00000524981.9 linkuse as main transcript	c.4539G>C	p.Met1513Ile	missense_variant	33/68	5	NM_001306084.2	P1	Q96N23-1
CFAP54	ENST00000637336.1 linkuse as main transcript	c.1257G>C	p.Met419Ile	missense_variant	10/46	5
CFAP54	ENST00000550977.2 linkuse as main transcript	c.780G>C	p.Met260Ile	missense_variant	7/8	5

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

134240

Hom.:

AF XY:

0.0000274

AC XY:

AN XY:

73118

show subpopulations

Gnomad AFR exome

AF:

0.000622

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:

0.0000190

Gnomad OTH exome

AF:

0.000485

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1375594

Hom.:

Cov.:

AF XY:

0.0000368

AC XY:

AN XY:

679454

show subpopulations

Gnomad4 AFR exome

AF:

0.000955

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000112

Gnomad4 OTH exome

AF:

0.0000347

GnomAD4 genome

AF:

0.000151

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000193

ExAC

AF:

0.0000648

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

CFAP54: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

DANN

Benign

0.55

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.43

M_CAP

Benign

0.0092

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.16

REVEL

Benign

0.069

Sift

Benign

0.45

Sift4G

Benign

0.49

Vest4

0.050

MutPred

0.34

Gain of sheet (P = 0.039);

MVP

0.030

MPC

0.043

ClinPred

0.0024

GERP RS

-2.5

Varity_R

0.065

gMVP

0.044

Splicing

Name

Calibrated prediction

Score

Prediction

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