14-94378547-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000295.5(SERPINA1):c.1159G>A(p.Glu387Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,770 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000295.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SERPINA1 | NM_000295.5 | c.1159G>A | p.Glu387Lys | missense_variant | 5/5 | ENST00000393087.9 | NP_000286.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000415 AC: 63AN: 151844Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000386 AC: 97AN: 251306Hom.: 0 AF XY: 0.000456 AC XY: 62AN XY: 135826
GnomAD4 exome AF: 0.000127 AC: 186AN: 1461808Hom.: 1 Cov.: 33 AF XY: 0.000151 AC XY: 110AN XY: 727214
GnomAD4 genome AF: 0.000408 AC: 62AN: 151962Hom.: 0 Cov.: 33 AF XY: 0.000633 AC XY: 47AN XY: 74290
ClinVar
Submissions by phenotype
Alpha-1-antitrypsin deficiency Uncertain:1Benign:3
Benign, no assertion criteria provided | curation | Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital | Dec 08, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Benign, no assertion criteria provided | literature only | GeneReviews | May 01, 2014 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 19, 2017 | - - |
SERPINA1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 30, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
PI CHRISTCHURCH Other:1
other, no assertion criteria provided | literature only | OMIM | Jul 15, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at