Variant 9-132498774-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001282957.2(CFAP77):c.275T>C(p.Leu92Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,610,248 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

CFAP77
NM_001282957.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.282

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026390761).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP77	NM_001282957.2 linkuse as main transcript	c.275T>C	p.Leu92Pro	missense_variant	2/6	ENST00000393216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP77	ENST00000393216.3 linkuse as main transcript	c.275T>C	p.Leu92Pro	missense_variant	2/6	1	NM_001282957.2	P1	Q6ZQR2-2
CFAP77	ENST00000343036.6 linkuse as main transcript	c.383T>C	p.Leu128Pro	missense_variant	3/7	2			Q6ZQR2-1
CFAP77	ENST00000393215.7 linkuse as main transcript	c.275T>C	p.Leu92Pro	missense_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000598

AC:

146

AN:

243996

Hom.:

AF XY:

0.000577

AC XY:

AN XY:

131774

show subpopulations

Gnomad AFR exome

AF:

0.000325

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000236

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000999

GnomAD4 exome

AF:

0.00117

AC:

1703

AN:

1457880

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

790

AN XY:

724774

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000414

Gnomad4 NFE exome

AF:

0.00146

Gnomad4 OTH exome

AF:

0.000747

GnomAD4 genome

AF:

0.000643

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000654

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000544

AC:

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

May 08, 2023

The c.383T>C (p.L128P) alteration is located in exon 3 (coding exon 3) of the CFAP77 gene. This alteration results from a T to C substitution at nucleotide position 383, causing the leucine (L) at amino acid position 128 to be replaced by a proline (P). 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

Benign

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

.;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.86

D;D;D

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.077

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.93, 0.47

.;P;P

Vest4

0.48

MVP

0.17

MPC

0.50

ClinPred

0.017

GERP RS

1.2

Varity_R

0.22

gMVP

0.65

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