rs763360042
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_139125.4(MASP1):c.870G>A(p.Trp290Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,996 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). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
MASP1
NM_139125.4 stop_gained
NM_139125.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.86
Genes affected
MASP1 (HGNC:6901): (MBL associated serine protease 1) This gene encodes a serine protease that functions as a component of the lectin pathway of complement activation. The complement pathway plays an essential role in the innate and adaptive immune response. The encoded protein is synthesized as a zymogen and is activated when it complexes with the pathogen recognition molecules of lectin pathway, the mannose-binding lectin and the ficolins. This protein is not directly involved in complement activation but may play a role as an amplifier of complement activation by cleaving complement C2 or by activating another complement serine protease, MASP-2. The encoded protein is also able to cleave fibrinogen and factor XIII and may may be involved in coagulation. A splice variant of this gene which lacks the serine protease domain functions as an inhibitor of the complement pathway. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-187253190-C-T is Pathogenic according to our data. Variant chr3-187253190-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 30078.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MASP1 | NM_139125.4 | c.870G>A | p.Trp290Ter | stop_gained | 6/11 | ENST00000296280.11 | NP_624302.1 | |
MASP1 | NM_001879.6 | c.870G>A | p.Trp290Ter | stop_gained | 6/16 | ENST00000337774.10 | NP_001870.3 | |
MASP1 | NM_001031849.3 | c.870G>A | p.Trp290Ter | stop_gained | 6/9 | NP_001027019.1 | ||
MASP1 | NR_033519.2 | n.743G>A | non_coding_transcript_exon_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MASP1 | ENST00000296280.11 | c.870G>A | p.Trp290Ter | stop_gained | 6/11 | 1 | NM_139125.4 | ENSP00000296280 | ||
MASP1 | ENST00000337774.10 | c.870G>A | p.Trp290Ter | stop_gained | 6/16 | 1 | NM_001879.6 | ENSP00000336792 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251436Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727216
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
3MC syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 15, 2012 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A;A
Vest4
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at