rs5935
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000312.4(PROC):c.891C>T(p.Asp297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,614,176 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 11 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 79 hom. )
Consequence
PROC
NM_000312.4 synonymous
NM_000312.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.20
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 2-127428451-C-T is Benign according to our data. Variant chr2-127428451-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 237634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=3.2 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00225 (343/152350) while in subpopulation EAS AF= 0.0411 (213/5180). AF 95% confidence interval is 0.0366. There are 11 homozygotes in gnomad4. There are 198 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 11 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROC | NM_000312.4 | c.891C>T | p.Asp297= | synonymous_variant | 9/9 | ENST00000234071.8 | |
LOC105373608 | XR_007087228.1 | n.1041-187G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROC | ENST00000234071.8 | c.891C>T | p.Asp297= | synonymous_variant | 9/9 | 1 | NM_000312.4 | P1 | |
PROC | ENST00000409048.1 | c.993C>T | p.Asp331= | synonymous_variant | 7/7 | 5 | |||
PROC | ENST00000402125.2 | c.216C>T | p.Asp72= | synonymous_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00228 AC: 347AN: 152232Hom.: 11 Cov.: 33
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GnomAD3 exomes AF: 0.00562 AC: 1412AN: 251386Hom.: 27 AF XY: 0.00600 AC XY: 816AN XY: 135896
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GnomAD4 exome AF: 0.00250 AC: 3661AN: 1461826Hom.: 79 Cov.: 31 AF XY: 0.00288 AC XY: 2098AN XY: 727216
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GnomAD4 genome ? AF: 0.00225 AC: 343AN: 152350Hom.: 11 Cov.: 33 AF XY: 0.00266 AC XY: 198AN XY: 74502
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
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 | 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at