rs121918157
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_000312.4(PROC):āc.1335C>Gā(p.Ile445Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I445L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000312.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROC | NM_000312.4 | c.1335C>G | p.Ile445Met | missense_variant | 9/9 | ENST00000234071.8 | |
LOC105373608 | XR_007087228.1 | n.1041-631G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROC | ENST00000234071.8 | c.1335C>G | p.Ile445Met | missense_variant | 9/9 | 1 | NM_000312.4 | P1 | |
PROC | ENST00000409048.1 | c.1437C>G | p.Ile479Met | missense_variant | 7/7 | 5 | |||
PROC | ENST00000402125.2 | c.660C>G | p.Ile220Met | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250760Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135542
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461668Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727150
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Thrombophilia due to protein C deficiency, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 15, 1993 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at