chr10-132812877-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001200049.3(CFAP46):​c.7409C>T​(p.Ala2470Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,609,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CFAP46
NM_001200049.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.368
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042352468).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFAP46NM_001200049.3 linkuse as main transcriptc.7409C>T p.Ala2470Val missense_variant 55/58 ENST00000368586.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFAP46ENST00000368586.10 linkuse as main transcriptc.7409C>T p.Ala2470Val missense_variant 55/585 NM_001200049.3 A2Q8IYW2-1
CFAP46ENST00000639072.2 linkuse as main transcriptc.7409C>T p.Ala2470Val missense_variant 55/595 P3

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152166
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000981
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000453
AC:
11
AN:
242824
Hom.:
0
AF XY:
0.0000604
AC XY:
8
AN XY:
132368
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
17
AN:
1456842
Hom.:
0
Cov.:
32
AF XY:
0.0000124
AC XY:
9
AN XY:
724918
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152166
Hom.:
0
Cov.:
34
AF XY:
0.000121
AC XY:
9
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000981
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000144
ExAC
AF:
0.0000165
AC:
2

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 GeneticsNov 10, 2022The c.2345C>T (p.A782V) alteration is located in exon 20 (coding exon 20) of the CFAP46 gene. This alteration results from a C to T substitution at nucleotide position 2345, causing the alanine (A) at amino acid position 782 to be replaced by a valine (V). 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
0.081
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
13
DANN
Benign
0.76
DEOGEN2
Benign
0.0066
T
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.00068
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.030
N
REVEL
Benign
0.018
Sift
Benign
0.61
T
Sift4G
Benign
0.16
T
Vest4
0.060
MVP
0.014
MPC
0.11
ClinPred
0.010
T
GERP RS
-0.59
Varity_R
0.027
gMVP
0.047

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: rs764849110; hg19: chr10-134626381; API