rs3138521

Variant names:

• chr1-173917605-CTAACCAAGGAAACAAACTTGGTTCATACCCA-TACCTGACTGAGGAGAAACTTGTCTGCAGGATTTTTTGTTTCTCGTTAACTAAATCAGAAGATAGAAATAGTTAATGTCCAAAAACTTCTAGCCCTCTACCTGTAATT
• rs3138521
• ENST00000812169.1:n.118+665_118+696delCTAACCAAGGAAACAAACTTGGTTCATACCCAinsTACCTGACTGAGGAGAAACTTGTCTGCAGGATTTTTTGTTTCTCGTTAACTAAATCAGAAGATAGAAATAGTTAATGTCCAAAAACTTCTAGCCCTCTACCTGTAATT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000812169.1(ENSG00000305649):​n.118+665_118+696delCTAACCAAGGAAACAAACTTGGTTCATACCCAinsTACCTGACTGAGGAGAAACTTGTCTGCAGGATTTTTTGTTTCTCGTTAACTAAATCAGAAGATAGAAATAGTTAATGTCCAAAAACTTCTAGCCCTCTACCTGTAATT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: ENSG00000305649 ENST00000812169.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 9 publications found

Genes affected

ENSG00000305649 (HGNC:):

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]

SERPINC1 Gene-Disease associations (from GenCC):

• hereditary antithrombin deficiency

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000812169.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000305649	ENST00000812169.1		n.118+665_118+696delCTAACCAAGGAAACAAACTTGGTTCATACCCAinsTACCTGACTGAGGAGAAACTTGTCTGCAGGATTTTTTGTTTCTCGTTAACTAAATCAGAAGATAGAAATAGTTAATGTCCAAAAACTTCTAGCCCTCTACCTGTAATT		intron	N/A
	ENSG00000305649	ENST00000812170.1		n.71+665_71+696delCTAACCAAGGAAACAAACTTGGTTCATACCCAinsTACCTGACTGAGGAGAAACTTGTCTGCAGGATTTTTTGTTTCTCGTTAACTAAATCAGAAGATAGAAATAGTTAATGTCCAAAAACTTCTAGCCCTCTACCTGTAATT		intron	N/A
	SERPINC1	ENST00000874324.1		c.-377_-346delTGGGTATGAACCAAGTTTGTTTCCTTGGTTAGinsAATTACAGGTAGAGGGCTAGAAGTTTTTGGACATTAACTATTTCTATCTTCTGATTTAGTTAACGAGAAACAAAAAATCCTGCAGACAAGTTTCTCCTCAGTCAGGTA		upstream_gene	N/A	ENSP00000544383.1

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3138521; hg19: chr1-173886743;