NM_002615.7:c.77dupC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_002615.7(SERPINF1):c.77dupC(p.Glu27GlyfsTer38) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,403,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P26P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Consequence
SERPINF1
NM_002615.7 frameshift
NM_002615.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.137
Publications
1 publications found
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]
SERPINF1 Gene-Disease associations (from GenCC):
- osteogenesis imperfecta type 6Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- osteogenesis imperfecta type 3Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteogenesis imperfecta type 4Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 47 pathogenic variants in the truncated region.
PP5
Variant 17-1766981-G-GC is Pathogenic according to our data. Variant chr17-1766981-G-GC is described in ClinVar as Pathogenic. ClinVar VariationId is 1342706.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002615.7. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SERPINF1 | NM_002615.7 | MANE Select | c.77dupC | p.Glu27GlyfsTer38 | frameshift | Exon 2 of 8 | NP_002606.3 | ||
| SERPINF1 | NM_001329903.2 | c.77dupC | p.Glu27GlyfsTer38 | frameshift | Exon 2 of 8 | NP_001316832.1 | A0A140VKF3 | ||
| SERPINF1 | NM_001329904.2 | c.-477-2865dupC | intron | N/A | NP_001316833.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SERPINF1 | ENST00000254722.9 | TSL:1 MANE Select | c.77dupC | p.Glu27GlyfsTer38 | frameshift | Exon 2 of 8 | ENSP00000254722.4 | P36955 | |
| SERPINF1 | ENST00000869424.1 | c.77dupC | p.Glu27GlyfsTer38 | frameshift | Exon 2 of 8 | ENSP00000539483.1 | |||
| SERPINF1 | ENST00000869426.1 | c.77dupC | p.Glu27GlyfsTer38 | frameshift | Exon 2 of 8 | ENSP00000539485.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000314 AC: 5AN: 159262 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
5
AN:
159262
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000499 AC: 7AN: 1403220Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2AN XY: 692532 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
7
AN:
1403220
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
692532
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31912
American (AMR)
AF:
AC:
0
AN:
36180
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
25194
East Asian (EAS)
AF:
AC:
1
AN:
36298
South Asian (SAS)
AF:
AC:
0
AN:
79482
European-Finnish (FIN)
AF:
AC:
1
AN:
49314
Middle Eastern (MID)
AF:
AC:
0
AN:
5504
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1081220
Other (OTH)
AF:
AC:
0
AN:
58116
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000102105), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.368
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Osteogenesis imperfecta type 6 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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