rs2227624
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2
The NM_000488.4(SERPINC1):c.89T>A(p.Val30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,614,198 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V30M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000488.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINC1 | NM_000488.4 | c.89T>A | p.Val30Glu | missense_variant | 2/7 | ENST00000367698.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINC1 | ENST00000367698.4 | c.89T>A | p.Val30Glu | missense_variant | 2/7 | 1 | NM_000488.4 | P1 | |
SERPINC1 | ENST00000494024.1 | n.315T>A | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00167 AC: 254AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00179 AC: 449AN: 251250Hom.: 2 AF XY: 0.00177 AC XY: 240AN XY: 135800
GnomAD4 exome AF: 0.00272 AC: 3983AN: 1461866Hom.: 14 Cov.: 31 AF XY: 0.00260 AC XY: 1894AN XY: 727236
GnomAD4 genome ? AF: 0.00167 AC: 254AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.00162 AC XY: 121AN XY: 74490
ClinVar
Submissions by phenotype
Hereditary antithrombin deficiency Pathogenic:2Uncertain:2Benign:2
Pathogenic, no assertion criteria provided | clinical testing | Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | Oct 30, 2023 | - - |
Uncertain significance, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Feb 01, 2019 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 1992 | - - |
Benign, 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
not provided Pathogenic:2Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 17, 2021 | Reported as AT Dublin in the literature (Daly et al., 1987); Published functional studies demonstrate impaired secretion and negligible inhibitory activity (Daly et al., 1990; Navarro-Fernndez et al., 2016).; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 1977621, 1483705, 31064749, 31894660, 29450643, 31885188, 28607330, 3472589, 23910795, 25496998, 24121110, 27098529, 31157679, 30721820) - |
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | SERPINC1: PS4, PM1, PP1, BP4 - |
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 01, 2022 | PP1_strong, PM1, PS3 - |
Thromboembolism Uncertain:1
Uncertain significance, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Feb 01, 2019 | - - |
Deep venous thrombosis Uncertain:1
Uncertain significance, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Feb 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at