chr12-121921636-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_144668.6(CFAP251):c.331G>T(p.Glu111Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,612,264 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.00098 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0022 ( 6 hom. )
Consequence
CFAP251
NM_144668.6 stop_gained
NM_144668.6 stop_gained
Scores
2
5
Clinical Significance
Conservation
PhyloP100: 0.367
Genes affected
CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 12-121921636-G-T is Pathogenic according to our data. Variant chr12-121921636-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 548449.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFAP251 | NM_144668.6 | c.331G>T | p.Glu111Ter | stop_gained | 2/22 | ENST00000288912.9 | |
CFAP251 | NM_001178003.2 | c.331G>T | p.Glu111Ter | stop_gained | 2/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP251 | ENST00000288912.9 | c.331G>T | p.Glu111Ter | stop_gained | 2/22 | 1 | NM_144668.6 | ||
CFAP251 | ENST00000397454.2 | c.331G>T | p.Glu111Ter | stop_gained | 2/18 | 1 | P1 | ||
CFAP251 | ENST00000540779.1 | n.229G>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000979 AC: 149AN: 152150Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.00100 AC: 248AN: 247336Hom.: 0 AF XY: 0.000998 AC XY: 134AN XY: 134204
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GnomAD4 exome AF: 0.00216 AC: 3154AN: 1459996Hom.: 6 Cov.: 37 AF XY: 0.00208 AC XY: 1513AN XY: 726252
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spermatogenic failure 33 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 04, 2024 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | Nov 24, 2023 | - - |
Non-syndromic male infertility due to sperm motility disorder;C4706677:Male infertility with teratozoospermia due to single gene mutation Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Marseille Medical Genetics, U1251, Aix Marseille University, Inserm | Jun 29, 2018 | Bialleleic rare loss-of-function variants in WDR66 have been described in two independent cases of asthenozoospermia with multiple morphologic abnormalities of the sperm flagellum. One of these cases is a compound heterozygote for p.Leu530Valfs*4 and a nonsense variant p.Glu111*. In this case a dysplasia of the mitochondrial sheath was described by immunofluorescence and electron microscopy (Auguste et al. 2018, article in revision). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;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