Variant 9-132499467-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282957.2(CFAP77):c.391G>C(p.Gly131Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,614,206 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G131S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CFAP77
NM_001282957.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

Variant links:

Genes affected

CFAP77 (HGNC:33776): (cilia and flagella associated protein 77) Predicted to be located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

CFAP77 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15178022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP77	NM_001282957.2 linkuse as main transcript	c.391G>C	p.Gly131Arg	missense_variant	3/6	ENST00000393216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP77	ENST00000393216.3 linkuse as main transcript	c.391G>C	p.Gly131Arg	missense_variant	3/6	1	NM_001282957.2	P1	Q6ZQR2-2
CFAP77	ENST00000343036.6 linkuse as main transcript	c.499G>C	p.Gly167Arg	missense_variant	4/7	2			Q6ZQR2-1
CFAP77	ENST00000393215.7 linkuse as main transcript	c.391G>C	p.Gly131Arg	missense_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

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:

0.000191

AC:

AN:

251428

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00250

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:

0.0000335

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000125

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000125

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.499G>C (p.G167R) alteration is located in exon 4 (coding exon 4) of the CFAP77 gene. This alteration results from a G to C substitution at nucleotide position 499, causing the glycine (G) at amino acid position 167 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

.;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.70

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Pathogenic

-7.4

D;D;D

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.88

MVP

0.49

MPC

0.62

ClinPred

0.37

GERP RS

5.3

Varity_R

0.82

gMVP

0.85

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