Variant 12-96630637-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001306084.2(CFAP54):c.4302G>C(p.Met1434Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,491,324 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 3 hom. )

Consequence

CFAP54
NM_001306084.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.331

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041428506).

BP6

Variant 12-96630637-G-C is Benign according to our data. Variant chr12-96630637-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2672515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP54	NM_001306084.2 linkuse as main transcript	c.4302G>C	p.Met1434Ile	missense_variant	32/68	ENST00000524981.9
CFAP54	NM_001367885.1 linkuse as main transcript	c.4302G>C	p.Met1434Ile	missense_variant	32/69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP54	ENST00000524981.9 linkuse as main transcript	c.4302G>C	p.Met1434Ile	missense_variant	32/68	5	NM_001306084.2	P1	Q96N23-1
CFAP54	ENST00000637336.1 linkuse as main transcript	c.1020G>C	p.Met340Ile	missense_variant	9/46	5
CFAP54	ENST00000550977.2 linkuse as main transcript	c.543G>C	p.Met181Ile	missense_variant	6/8	5
CFAP54	ENST00000554108.6 linkuse as main transcript	n.2276G>C		non_coding_transcript_exon_variant	18/19	5

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000703

AC:

AN:

105192

Hom.:

AF XY:

0.000725

AC XY:

AN XY:

57918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00720

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000487

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000204

Gnomad OTH exome

AF:

0.000926

GnomAD4 exome

AF:

0.000320

AC:

428

AN:

1339216

Hom.:

Cov.:

AF XY:

0.000357

AC XY:

236

AN XY:

660682

show subpopulations

Gnomad4 AFR exome

AF:

0.0000344

Gnomad4 AMR exome

AF:

0.000286

Gnomad4 ASJ exome

AF:

0.00739

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.0000300

Gnomad4 NFE exome

AF:

0.000124

Gnomad4 OTH exome

AF:

0.000981

GnomAD4 genome

AF:

0.000243

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00117

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3474

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

Uncertain

0.40

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.6

DANN

Benign

0.61

DEOGEN2

Benign

0.017

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.43

M_CAP

Benign

0.0037

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.71

REVEL

Benign

0.017

Sift

Benign

0.19

Sift4G

Benign

0.31

Vest4

0.11

MutPred

0.30

Gain of catalytic residue at M1434 (P = 0.0451);

MVP

0.040

MPC

0.039

ClinPred

0.0065

GERP RS

3.4

Varity_R

0.079

gMVP

0.086

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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