rs61757459
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_001382267.1(SERPINA12):c.631C>T(p.Arg211Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00714 in 1,600,876 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0074 ( 53 hom. )
Consequence
SERPINA12
NM_001382267.1 stop_gained
NM_001382267.1 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 4.32
Genes affected
SERPINA12 (HGNC:18359): (serpin family A member 12) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within negative regulation of gluconeogenesis; positive regulation of signal transduction; and regulation of lipid metabolic process. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
?
Variant 14-94497767-G-A is Benign according to our data. Variant chr14-94497767-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2574603.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA12 | NM_001382267.1 | c.631C>T | p.Arg211Ter | stop_gained | 2/5 | ENST00000677451.1 | |
SERPINA12 | NM_001304461.2 | c.631C>T | p.Arg211Ter | stop_gained | 2/5 | ||
SERPINA12 | NM_173850.4 | c.631C>T | p.Arg211Ter | stop_gained | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA12 | ENST00000677451.1 | c.631C>T | p.Arg211Ter | stop_gained | 2/5 | NM_001382267.1 | P1 | ||
SERPINA12 | ENST00000341228.2 | c.631C>T | p.Arg211Ter | stop_gained | 3/6 | 1 | P1 | ||
SERPINA12 | ENST00000556881.5 | c.631C>T | p.Arg211Ter | stop_gained | 2/5 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00495 AC: 753AN: 152102Hom.: 5 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00510 AC: 1235AN: 242086Hom.: 5 AF XY: 0.00498 AC XY: 651AN XY: 130694
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GnomAD4 exome AF: 0.00737 AC: 10680AN: 1448656Hom.: 53 Cov.: 32 AF XY: 0.00706 AC XY: 5082AN XY: 719408
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GnomAD4 genome ? AF: 0.00495 AC: 753AN: 152220Hom.: 5 Cov.: 32 AF XY: 0.00453 AC XY: 337AN XY: 74402
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ClinVar
Significance: Likely benign
Submissions summary: Pathogenic:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary palmoplantar keratoderma, Gamborg-Nielsen type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Institute for Human Genetics, University Medical Center Freiburg | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | SERPINA12: BS2 - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at