rs764220898
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_000295.5(SERPINA1):āc.745G>Cā(p.Gly249Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ā ). Synonymous variant affecting the same amino acid position (i.e. G249G) has been classified as Likely benign.
Frequency
Consequence
NM_000295.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA1 | NM_000295.5 | c.745G>C | p.Gly249Arg | missense_variant | 3/5 | ENST00000393087.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA1 | ENST00000393087.9 | c.745G>C | p.Gly249Arg | missense_variant | 3/5 | 1 | NM_000295.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152062Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251410Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135872
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74280
ClinVar
Submissions by phenotype
Alpha-1-antitrypsin deficiency Pathogenic:2Uncertain:1
Uncertain significance, 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 | literature only | Counsyl | Oct 15, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 15, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at