chr14-94379500-GGA-G
Position:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000295.5(SERPINA1):c.1027_1028del(p.Ser343ArgfsTer16) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic,other (no stars). Synonymous variant affecting the same amino acid position (i.e. S343S) has been classified as Benign.
Frequency
Genomes: not found (cov: 34)
Consequence
SERPINA1
NM_000295.5 frameshift
NM_000295.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.33
Genes affected
SERPINA1 (HGNC:8941): (serpin family A member 1) The protein encoded by this gene is a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. This protein is produced in the liver, the bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut. Defects in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 24 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-94379500-GGA-G is Pathogenic according to our data. Variant chr14-94379500-GGA-G is described in ClinVar as [Pathogenic, other]. Clinvar id is 17980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-94379500-GGA-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA1 | NM_000295.5 | c.1027_1028del | p.Ser343ArgfsTer16 | frameshift_variant | 4/5 | ENST00000393087.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA1 | ENST00000393087.9 | c.1027_1028del | p.Ser343ArgfsTer16 | frameshift_variant | 4/5 | 1 | NM_000295.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Pathogenic; other
Submissions summary: Pathogenic:1Other:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Alpha-1-antitrypsin deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | GeneReviews | May 01, 2014 | - - |
PI Q0(HONG KONG 1) Other:1
other, no assertion criteria provided | literature only | OMIM | Jul 20, 2016 | - - |
PI NULL(HONG KONG 1) Other:1
other, no assertion criteria provided | literature only | OMIM | Jul 20, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at