rs375801610
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_145020.5(CFAP53):c.121C>T(p.Arg41Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,002 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
CFAP53
NM_145020.5 stop_gained
NM_145020.5 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 1.00
Genes affected
CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 18-50262168-G-A is Pathogenic according to our data. Variant chr18-50262168-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 208550.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr18-50262168-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFAP53 | NM_145020.5 | c.121C>T | p.Arg41Ter | stop_gained | 2/8 | ENST00000398545.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP53 | ENST00000398545.5 | c.121C>T | p.Arg41Ter | stop_gained | 2/8 | 1 | NM_145020.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249560Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135390
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727238
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74294
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Heterotaxy, visceral, 6, autosomal Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2015 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A
Vest4
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at