10-132814242-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001200049.3(CFAP46):​c.7298C>T​(p.Pro2433Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CFAP46
NM_001200049.3 missense

Scores

4
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.892
Variant links:
Genes affected
CFAP46 (HGNC:25247): (cilia and flagella associated protein 46) Predicted to be involved in axoneme assembly. Predicted to be located in axoneme. [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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFAP46NM_001200049.3 linkuse as main transcriptc.7298C>T p.Pro2433Leu missense_variant 54/58 ENST00000368586.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFAP46ENST00000368586.10 linkuse as main transcriptc.7298C>T p.Pro2433Leu missense_variant 54/585 NM_001200049.3 A2Q8IYW2-1
CFAP46ENST00000639072.2 linkuse as main transcriptc.7298C>T p.Pro2433Leu missense_variant 54/595 P3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248044
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134606
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00000137
AC:
2
AN:
1460940
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726776
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 GeneticsApr 05, 2023The c.2234C>T (p.P745L) alteration is located in exon 19 (coding exon 19) of the CFAP46 gene. This alteration results from a C to T substitution at nucleotide position 2234, causing the proline (P) at amino acid position 745 to be replaced by a leucine (L). 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
Pathogenic
0.67
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.087
T
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.087
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.055
D
MetaRNN
Pathogenic
0.74
D
MetaSVM
Benign
-0.72
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Benign
0.24
Sift
Uncertain
0.0040
D
Sift4G
Pathogenic
0.0
D
Vest4
0.64
MVP
0.23
MPC
0.54
ClinPred
0.91
D
GERP RS
4.3
Varity_R
0.20
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs757325575; hg19: chr10-134627746; COSMIC: COSV54153573; COSMIC: COSV54153573; API