NM_003784.4:c.54_55delGA
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_003784.4(SERPINB7):c.54_55delGA(p.Glu18AspfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SERPINB7
NM_003784.4 frameshift
NM_003784.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.673
Publications
0 publications found
Genes affected
SERPINB7 (HGNC:13902): (serpin family B member 7) This gene encodes a member of a family of proteins which function as protease inhibitors. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
SERPINB7 Gene-Disease associations (from GenCC):
- palmoplantar keratoderma, Nagashima typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 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 8 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 18-63782420-CAG-C is Pathogenic according to our data. Variant chr18-63782420-CAG-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3049966.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003784.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| SERPINB7 | NM_003784.4 | MANE Select | c.54_55delGA | p.Glu18AspfsTer3 | frameshift | Exon 2 of 8 | NP_003775.1 | O75635-1 | |
| SERPINB7 | NM_001040147.3 | c.54_55delGA | p.Glu18AspfsTer3 | frameshift | Exon 2 of 8 | NP_001035237.1 | O75635-1 | ||
| SERPINB7 | NM_001261830.2 | c.54_55delGA | p.Glu18AspfsTer3 | frameshift | Exon 2 of 8 | NP_001248759.1 | O75635-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SERPINB7 | ENST00000398019.7 | TSL:1 MANE Select | c.54_55delGA | p.Glu18AspfsTer3 | frameshift | Exon 2 of 8 | ENSP00000381101.2 | O75635-1 | |
| SERPINB7 | ENST00000336429.6 | TSL:1 | c.54_55delGA | p.Glu18AspfsTer3 | frameshift | Exon 2 of 8 | ENSP00000337212.2 | O75635-1 | |
| SERPINB7 | ENST00000546027.5 | TSL:2 | c.54_55delGA | p.Glu18AspfsTer3 | frameshift | Exon 2 of 8 | ENSP00000444861.1 | O75635-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461826Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727202 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461826
Hom.:
AF XY:
AC XY:
2
AN XY:
727202
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
2
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111982
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
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:Likely pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
SERPINB7-related disorder (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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