9-121074757-CA-C
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001317163.2(C5):c.79delT(p.Cys27AlafsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 301,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Consequence
NM_001317163.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C5 | NM_001317163.2 | c.79delT | p.Cys27AlafsTer20 | frameshift_variant | Exon 1 of 41 | NP_001304092.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C5 | ENST00000696281.1 | c.79delT | p.Cys27AlafsTer20 | frameshift_variant | Exon 1 of 42 | ENSP00000512521.1 | ||||
CNTRL | ENST00000690496.1 | n.-513delA | non_coding_transcript_exon_variant | Exon 1 of 18 | ENSP00000508719.1 | |||||
C5 | ENST00000696279.1 | n.40delT | non_coding_transcript_exon_variant | Exon 1 of 43 | ENSP00000512520.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000785 AC: 1AN: 127400Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 69742
GnomAD4 exome AF: 0.00000332 AC: 1AN: 301028Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 171520
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
The C5 p.C27fs variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs1362872776) and in control databases in 1 of 127400 chromosomes at a frequency of 0.000007849 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 1 of 47176 chromosomes (freq: 0.000021), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The c.79delT variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 27 and leads to a premature stop codon. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the C5 gene are an established mechanism of disease in C5 deficiency and is the type of variant expected to cause the disorder when found in the homozygous or compound heterozygous state. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at