Variant rs76722120 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_145020.5(CFAP53):c.305G>C(p.Arg102Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,323,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFAP53
NM_145020.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

CFAP53 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP53	NM_145020.5 linkuse as main transcript	c.305G>C	p.Arg102Pro	missense_variant	3/8	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 linkuse as main transcript	c.305G>C	p.Arg102Pro	missense_variant	3/8	1	NM_145020.5	ENSP00000381553	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

138416

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000701

AC:

AN:

142736

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000942

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000151

AC:

AN:

1323144

Hom.:

Cov.:

AF XY:

0.00000306

AC XY:

AN XY:

652702

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000450

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:

9.50e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

138416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66204

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.20

Sift

Uncertain

0.016

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.73

MutPred

0.27

Gain of glycosylation at R102 (P = 0.0663);

MVP

0.50

MPC

0.45

ClinPred

0.94

GERP RS

6.1

Varity_R

0.80

gMVP

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over