rs200460215
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000488.4(SERPINC1):c.-35C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000231 in 1,604,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
SERPINC1
NM_000488.4 5_prime_UTR
NM_000488.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.03
Genes affected
SERPINC1 (HGNC:775): (serpin family C member 1) The protein encoded by this gene, antithrombin III, is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. Numerous mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency which constitutes a strong risk factor for thrombosis. A reduction in the serum level of this protein is associated with severe cases of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Sep 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINC1 | NM_000488.4 | c.-35C>T | 5_prime_UTR_variant | 1/7 | ENST00000367698.4 | ||
LOC124904457 | XR_007066739.1 | n.441+354G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINC1 | ENST00000367698.4 | c.-35C>T | 5_prime_UTR_variant | 1/7 | 1 | NM_000488.4 | P1 | ||
SERPINC1 | ENST00000494024.1 | n.23C>T | non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000120 AC: 30AN: 250124Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 135092
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GnomAD4 exome AF: 0.0000227 AC: 33AN: 1452584Hom.: 0 Cov.: 27 AF XY: 0.0000235 AC XY: 17AN XY: 723128
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74476
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Tuberous sclerosis 2 Other:1
not provided, no classification provided | literature only | Hubei Clinical and Research Center of Thrombosis and Hemostasis Institute of Hematology, Union Hospital | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at