rs1554862953
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1_ModeratePM2PP3_StrongPP5
The NM_025145.7(CFAP43):c.3541-2A>C variant causes a splice acceptor change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CFAP43
NM_025145.7 splice_acceptor
NM_025145.7 splice_acceptor
Scores
4
2
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 6.45
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.023809524 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.5, offset of 7, new splice context is: gttttccttttcgtcattAGaag. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 10-104152728-T-G is Pathogenic according to our data. Variant chr10-104152728-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 523145.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-104152728-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFAP43 | NM_025145.7 | c.3541-2A>C | splice_acceptor_variant | ENST00000357060.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP43 | ENST00000357060.8 | c.3541-2A>C | splice_acceptor_variant | 1 | NM_025145.7 | P1 | |||
CFAP43 | ENST00000434629.5 | c.1623-2A>C | splice_acceptor_variant | 1 | |||||
CFAP43 | ENST00000457071.5 | c.87-2A>C | splice_acceptor_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spermatogenic failure 19 Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Strasbourg University Hospital | Feb 09, 2021 | Homozygous splice site variant "c.3541-2A>C" was reported before in 2 unrelated Tunisian patients for sperm flagella problems (Coutton et al 2018, doi.org/10.1038/s41467-017-02792-7). Our patient is a Moroccan man suffering infertility due to a sperm flagellar problem. - |
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
D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -9
DS_AL_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at