rs866096259
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001164496.2(CFAP44):c.1387G>T(p.Glu463Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000343 in 1,458,894 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CFAP44
NM_001164496.2 stop_gained
NM_001164496.2 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.04
Genes affected
CFAP44 (HGNC:25631): (cilia and flagella associated protein 44) Enables peptidase activity. Involved in sperm axoneme assembly. Acts upstream of or within microtubule cytoskeleton organization. Predicted to be located in cytoplasm; cytoskeleton; and motile cilium. Implicated in spermatogenic failure 20. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 3-113400632-C-A is Pathogenic according to our data. Variant chr3-113400632-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 523152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-113400632-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFAP44 | NM_001164496.2 | c.1387G>T | p.Glu463Ter | stop_gained | 12/35 | ENST00000393845.9 | |
LOC127898559 | NR_183046.1 | n.4668G>T | non_coding_transcript_exon_variant | 29/48 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP44 | ENST00000393845.9 | c.1387G>T | p.Glu463Ter | stop_gained | 12/35 | 5 | NM_001164496.2 | P2 | |
CFAP44 | ENST00000295868.6 | c.1387G>T | p.Glu463Ter | stop_gained | 12/21 | 1 | A2 | ||
CFAP44 | ENST00000465186.1 | c.*35G>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/4 | 5 | ||||
CFAP44 | ENST00000488854.6 | c.*803G>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/16 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458894Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725692
GnomAD4 exome
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5
AN:
1458894
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30
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3
AN XY:
725692
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spermatogenic failure 20 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics, First Genomix Laboratory | Jul 04, 2022 | First Genomix Laboratory has identified this variant in a homozygous state in a patient presenting with immotile sperm and Glucose-6-Phosphate Dehydrogenase Deficiency. In addition, this variant was identified in a heterozygous state in an unaffected patient. Coutton et al., 2018 have identified this variant in a homozygous state in a patient presenting with primary infertility due to multiple morphological abnormalities of the flagella (PMID: 29449551). - |
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 02, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at