Variant 9-132410303-T-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_001282957.2(CFAP77):c.32T>C(p.Leu11Pro) 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 1,592,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

CFAP77
NM_001282957.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

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 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=0.012029886).

BP6

Variant 9-132410303-T-C is Benign according to our data. Variant chr9-132410303-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2473294.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP77	NM_001282957.2 linkuse as main transcript	c.32T>C	p.Leu11Pro	missense_variant	1/6	ENST00000393216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP77	ENST00000393216.3 linkuse as main transcript	c.32T>C	p.Leu11Pro	missense_variant	1/6	1	NM_001282957.2	P1	Q6ZQR2-2
CFAP77	ENST00000343036.6 linkuse as main transcript	c.32T>C	p.Leu11Pro	missense_variant	1/7	2			Q6ZQR2-1
CFAP77	ENST00000393215.7 linkuse as main transcript	c.32T>C	p.Leu11Pro	missense_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000956

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

208672

Hom.:

AF XY:

0.0000258

AC XY:

AN XY:

116106

show subpopulations

Gnomad AFR exome

AF:

0.000840

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000257

AC:

AN:

1440436

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

715878

show subpopulations

Gnomad4 AFR exome

AF:

0.000833

Gnomad4 AMR exome

AF:

0.000140

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:

0.00

Gnomad4 OTH exome

AF:

0.0000841

GnomAD4 genome

AF:

0.000263

AC:

AN:

151914

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.000846

Gnomad4 AMR

AF:

0.000196

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:

0.000956

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000952

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000676

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.8

DANN

Benign

0.89

DEOGEN2

Benign

0.0048

.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.73

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.089

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.17

MVP

0.030

MPC

0.20

ClinPred

0.017

GERP RS

-4.0

Varity_R

0.073

gMVP

0.24

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