chr14-94378547-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_000295.5(SERPINA1):βc.1158delβ(p.Glu387ArgfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. P386P) has been classified as Likely benign.
Frequency
Consequence
NM_000295.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA1 | NM_000295.5 | c.1158del | p.Glu387ArgfsTer11 | frameshift_variant | 5/5 | ENST00000393087.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA1 | ENST00000393087.9 | c.1158del | p.Glu387ArgfsTer11 | frameshift_variant | 5/5 | 1 | NM_000295.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151844Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251306Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135826
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461794Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727208
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151844Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74162
ClinVar
Submissions by phenotype
Alpha-1-antitrypsin deficiency Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 02, 2024 | - - |
Pathogenic, no assertion criteria provided | curation | Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital | Dec 08, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 10, 2022 | - - |
PI NULL(BOLTON) Other:1
other, no assertion criteria provided | literature only | OMIM | Jul 20, 2016 | - - |
PI Q0(BOLTON) Other:1
other, no assertion criteria provided | literature only | OMIM | Jul 20, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at