rs2254419

Variant summary

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

The NM_001200049.3(CFAP46):​c.7618A>T​(p.Ser2540Cys) 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. 14/20 in silico tools predict a benign 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. S2540G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CFAP46
NM_001200049.3 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.43
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.088825285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFAP46NM_001200049.3 linkuse as main transcriptc.7618A>T p.Ser2540Cys missense_variant 57/58 ENST00000368586.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFAP46ENST00000368586.10 linkuse as main transcriptc.7618A>T p.Ser2540Cys missense_variant 57/585 NM_001200049.3 A2Q8IYW2-1
CFAP46ENST00000639072.2 linkuse as main transcriptc.7755A>T p.Thr2585= synonymous_variant 58/595 P3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461316
Hom.:
0
Cov.:
57
AF XY:
0.00000138
AC XY:
1
AN XY:
726960
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.052
DANN
Benign
0.72
DEOGEN2
Benign
0.013
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.28
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.089
T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.89
N
REVEL
Benign
0.075
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.016
D
Vest4
0.14
MVP
0.014
MPC
0.21
ClinPred
0.39
T
GERP RS
-6.0
Varity_R
0.072
gMVP
0.064

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2254419; hg19: chr10-134623959; API