9-132537635-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001282957.2(CFAP77):​c.559C>T​(p.Arg187Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,380 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 (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

CFAP77
NM_001282957.2 missense

Scores

2
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3433469).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFAP77NM_001282957.2 linkuse as main transcriptc.559C>T p.Arg187Trp missense_variant 4/6 ENST00000393216.3
CFAP77NM_207417.3 linkuse as main transcriptc.667C>T p.Arg223Trp missense_variant 5/7
CFAP77XM_011518670.3 linkuse as main transcriptc.559C>T p.Arg187Trp missense_variant 4/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFAP77ENST00000393216.3 linkuse as main transcriptc.559C>T p.Arg187Trp missense_variant 4/61 NM_001282957.2 P1Q6ZQR2-2
CFAP77ENST00000343036.6 linkuse as main transcriptc.667C>T p.Arg223Trp missense_variant 5/72 Q6ZQR2-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000128
AC:
32
AN:
250582
Hom.:
0
AF XY:
0.000126
AC XY:
17
AN XY:
135440
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000468
Gnomad ASJ exome
AF:
0.000497
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000595
AC:
87
AN:
1461138
Hom.:
0
Cov.:
31
AF XY:
0.0000660
AC XY:
48
AN XY:
726850
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000403
Gnomad4 ASJ exome
AF:
0.000421
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000718
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000594

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 submitterclinical testingAmbry GeneticsSep 14, 2022The c.667C>T (p.R223W) alteration is located in exon 5 (coding exon 5) of the CFAP77 gene. This alteration results from a C to T substitution at nucleotide position 667, causing the arginine (R) at amino acid position 223 to be replaced by a tryptophan (W). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T;.
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-0.81
T
MutationTaster
Benign
0.62
D;D
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Benign
0.18
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;D
Vest4
0.61
MVP
0.66
MPC
0.58
ClinPred
0.38
T
GERP RS
4.4
Varity_R
0.40
gMVP
0.62

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.

Other links and lift over

dbSNP: rs182716958; hg19: chr9-135413022; COSMIC: COSV58011169; API