rs121912713
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_000295.5(SERPINA1):c.1145T>G(p.Met382Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
SERPINA1
NM_000295.5 missense
NM_000295.5 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 0.730
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 14-94378561-A-C is Pathogenic according to our data. Variant chr14-94378561-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 17982.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-94378561-A-C is described in Lovd as [Likely_pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27427423). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA1 | NM_000295.5 | c.1145T>G | p.Met382Arg | missense_variant | 5/5 | ENST00000393087.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA1 | ENST00000393087.9 | c.1145T>G | p.Met382Arg | missense_variant | 5/5 | 1 | NM_000295.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Alpha-1-antitrypsin deficiency Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | GeneReviews | May 01, 2014 | - - |
Pathogenic, no assertion criteria provided | curation | Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital | Dec 08, 2014 | - - |
Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 1995 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;T;T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L;L;L;L
MutationTaster
Benign
N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D;.;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;.;T;T;T
Sift4G
Benign
T;T;T;T;T;.;T;T;T
Polyphen
B;B;B;B;B;B;B;B;B
Vest4
MutPred
Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);Gain of catalytic residue at P385 (P = 2e-04);
MVP
MPC
0.061
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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