2-127419925-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000312.4(PROC):​c.-18G>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PROC
NM_000312.4 5_prime_UTR_premature_start_codon_gain

Scores

1
1
Splicing: ADA: 0.03572
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PROCNM_000312.4 linkc.-18G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 9 ENST00000234071.8 NP_000303.1 P04070-1
PROCNM_000312.4 linkc.-18G>T 5_prime_UTR_variant Exon 2 of 9 ENST00000234071.8 NP_000303.1 P04070-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PROCENST00000234071 linkc.-18G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 9 1 NM_000312.4 ENSP00000234071.4 P04070-1
PROCENST00000234071 linkc.-18G>T 5_prime_UTR_variant Exon 2 of 9 1 NM_000312.4 ENSP00000234071.4 P04070-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Feb 15, 2024
Mayo Clinic Laboratories, Mayo Clinic
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

PM2_moderate -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
18
DANN
Uncertain
0.99

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.036
SpliceAI score (max)
0.68
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.68
Position offset: -3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-128177501; API