chr4-185164155-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_020827.3(CFAP97):​c.1345G>T​(p.Val449Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V449M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CFAP97
NM_020827.3 missense

Scores

3
7
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.77

Publications

0 publications found
Variant links:
Genes affected
CFAP97 (HGNC:29276): (cilia and flagella associated protein 97)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFAP97NM_020827.3 linkc.1345G>T p.Val449Leu missense_variant Exon 4 of 5 ENST00000458385.7 NP_065878.1 Q9P2B7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFAP97ENST00000458385.7 linkc.1345G>T p.Val449Leu missense_variant Exon 4 of 5 2 NM_020827.3 ENSP00000409964.2 Q9P2B7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461538
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727048
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86224
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53390
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111792
Other (OTH)
AF:
0.00
AC:
0
AN:
60360
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.028
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.039
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-1.2
T
PhyloP100
4.8
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.17
Sift
Uncertain
0.012
D
Sift4G
Benign
0.078
T
Polyphen
1.0
D
Vest4
0.80
MutPred
0.47
Loss of methylation at K450 (P = 0.0454);
MVP
0.78
MPC
0.13
ClinPred
0.94
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.53
Mutation Taster
=75/25
polymorphism

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

Other links and lift over

dbSNP: rs372872250; hg19: chr4-186085309; API