rs398122520
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002615.7(SERPINF1):c.653del(p.Val218GlufsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
SERPINF1
NM_002615.7 frameshift
NM_002615.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.338
Genes affected
SERPINF1 (HGNC:8824): (serpin family F member 1) This gene encodes a member of the serpin family that does not display the serine protease inhibitory activity shown by many of the other serpin proteins. The encoded protein is secreted and strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells. Mutations in this gene were found in individuals with osteogenesis imperfecta, type VI. [provided by RefSeq, Aug 2016]
Genome browser will be placed here
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 17-1775066-GT-G is Pathogenic according to our data. Variant chr17-1775066-GT-G is described in ClinVar as [Pathogenic]. Clinvar id is 41894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1775066-GT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINF1 | NM_002615.7 | c.653del | p.Val218GlufsTer22 | frameshift_variant | 6/8 | ENST00000254722.9 | |
SERPINF1 | NM_001329903.2 | c.653del | p.Val218GlufsTer22 | frameshift_variant | 6/8 | ||
SERPINF1 | NM_001329904.2 | c.92del | p.Val31GlufsTer22 | frameshift_variant | 5/7 | ||
SERPINF1 | NM_001329905.2 | c.92del | p.Val31GlufsTer22 | frameshift_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINF1 | ENST00000254722.9 | c.653del | p.Val218GlufsTer22 | frameshift_variant | 6/8 | 1 | NM_002615.7 | P1 | |
SERPINF1 | ENST00000573763.1 | c.47del | p.Val16GlufsTer22 | frameshift_variant | 2/4 | 3 | |||
SERPINF1 | ENST00000572048.1 | c.92del | p.Val31GlufsTer22 | frameshift_variant | 2/3 | 2 | |||
SERPINF1 | ENST00000576406.5 | c.92del | p.Val31GlufsTer22 | frameshift_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2023 | This sequence change creates a premature translational stop signal (p.Val218Glufs*22) in the SERPINF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SERPINF1 are known to be pathogenic (PMID: 21353196, 21826736). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with osteogenesis imperfecta (PMID: 23054245, 29620724). ClinVar contains an entry for this variant (Variation ID: 41894). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 24, 2017 | - - |
Osteogenesis imperfecta type 6 Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare | Apr 20, 2017 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at