rs148855579
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000312.4(PROC):āc.1161T>Cā(p.Cys387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,728 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00062 ( 0 hom., cov: 33)
Exomes š: 0.0012 ( 22 hom. )
Consequence
PROC
NM_000312.4 synonymous
NM_000312.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.740
Genes affected
PROC (HGNC:9451): (protein C, inactivator of coagulation factors Va and VIIIa) This gene encodes a vitamin K-dependent plasma glycoprotein. The encoded protein is cleaved to its activated form by the thrombin-thrombomodulin complex. This activated form contains a serine protease domain and functions in degradation of the activated forms of coagulation factors V and VIII. Mutations in this gene have been associated with thrombophilia due to protein C deficiency, neonatal purpura fulminans, and recurrent venous thrombosis.[provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 2-127428721-T-C is Benign according to our data. Variant chr2-127428721-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 331112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.74 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00124 (1807/1461350) while in subpopulation SAS AF= 0.0144 (1244/86258). AF 95% confidence interval is 0.0138. There are 22 homozygotes in gnomad4_exome. There are 1239 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 22 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROC | NM_000312.4 | c.1161T>C | p.Cys387= | synonymous_variant | 9/9 | ENST00000234071.8 | |
LOC105373608 | XR_007087228.1 | n.1041-457A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROC | ENST00000234071.8 | c.1161T>C | p.Cys387= | synonymous_variant | 9/9 | 1 | NM_000312.4 | P1 | |
PROC | ENST00000409048.1 | c.1263T>C | p.Cys421= | synonymous_variant | 7/7 | 5 | |||
PROC | ENST00000402125.2 | c.486T>C | p.Cys162= | synonymous_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000630 AC: 96AN: 152260Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00219 AC: 551AN: 251068Hom.: 6 AF XY: 0.00295 AC XY: 400AN XY: 135794
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GnomAD4 exome AF: 0.00124 AC: 1807AN: 1461350Hom.: 22 Cov.: 31 AF XY: 0.00170 AC XY: 1239AN XY: 726992
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GnomAD4 genome ? AF: 0.000623 AC: 95AN: 152378Hom.: 0 Cov.: 33 AF XY: 0.000912 AC XY: 68AN XY: 74522
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Thrombophilia due to protein C deficiency, autosomal dominant Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | PROC: BP4, BP7, BS1, BS2 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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