9-132482338-C-T

Variant summary

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

The NM_207417.3(CFAP77):​c.224C>T​(p.Ser75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

CFAP77
NM_207417.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.137
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]

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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=0.080331415).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFAP77NM_001282957.2 linkc.196-16357C>T intron_variant Intron 1 of 5 ENST00000393216.3 NP_001269886.1 Q6ZQR2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFAP77ENST00000393216.3 linkc.196-16357C>T intron_variant Intron 1 of 5 1 NM_001282957.2 ENSP00000376909.2 Q6ZQR2-2
CFAP77ENST00000343036.6 linkc.224C>T p.Ser75Phe missense_variant Exon 2 of 7 2 ENSP00000343290.2 Q6ZQR2-1
CFAP77ENST00000393215.7 linkc.196-16357C>T intron_variant Intron 1 of 3 5 ENSP00000376908.3 A2A393

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.224C>T (p.S75F) alteration is located in exon 2 (coding exon 2) of the CFAP77 gene. This alteration results from a C to T substitution at nucleotide position 224, causing the serine (S) at amino acid position 75 to be replaced by a phenylalanine (F). 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
0.14
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
2.8
DANN
Benign
0.80
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-0.99
T
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.0090
Sift
Benign
0.068
T
Sift4G
Benign
0.086
T
Polyphen
0.021
B
Vest4
0.21
MutPred
0.39
Loss of disorder (P = 0.0019);
MVP
0.040
MPC
0.14
ClinPred
0.072
T
GERP RS
-0.29
Varity_R
0.039
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-135357725; API