rs574547491
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1BP4
This summary comes from the ClinGen Evidence Repository: The c.553A>G (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of threonine by alanine at amino acid 185 (p.Thr185Ala). The highest population minor allele frequency in gnomAD v2.1.1 is 0.001796 (55/30616 alleles) in the South Asian population, which is higher than the ClinGen SERPINC1 threshold ([>0.0002]) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.168, which is below the threshold of 0.3, and the splice site predictors VarSEAK and Splice AI indicated that the variant has no impact on splicing, which suggests that the variant does not impact SERPINC1 function (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BS1, BS4 LINK:https://erepo.genome.network/evrepo/ui/classification/CA1251401/MONDO:0013144/084
Frequency
Consequence
NM_000488.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINC1 | NM_000488.4 | c.553A>G | p.Thr185Ala | missense_variant | 3/7 | ENST00000367698.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINC1 | ENST00000367698.4 | c.553A>G | p.Thr185Ala | missense_variant | 3/7 | 1 | NM_000488.4 | P1 | |
SERPINC1 | ENST00000487183.1 | n.258A>G | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000219 AC: 55AN: 251482Hom.: 0 AF XY: 0.000331 AC XY: 45AN XY: 135918
GnomAD4 exome AF: 0.0000951 AC: 139AN: 1461880Hom.: 2 Cov.: 32 AF XY: 0.000151 AC XY: 110AN XY: 727242
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74460
ClinVar
Submissions by phenotype
Hereditary antithrombin deficiency Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
Likely benign, reviewed by expert panel | curation | Clingen Thrombosis Variant Curation Expert Panel, ClinGen | Jul 25, 2023 | The c.553A>G (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of threonine by alanine at amino acid 185 (p.Thr185Ala). The highest population minor allele frequency in gnomAD v2.1.1 is 0.001796 (55/30616 alleles) in the South Asian population, which is higher than the ClinGen SERPINC1 threshold ([>0.0002]) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.168, which is below the threshold of 0.3, and the splice site predictors VarSEAK and Splice AI indicated that the variant has no impact on splicing, which suggests that the variant does not impact SERPINC1 function (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BS1, BS4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at