rs763360042

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

Scores

5
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.86
Variant links:
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]

Genome browser will be placed here

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
MASP1NM_139125.4 linkuse as main transcriptc.870G>A p.Trp290Ter stop_gained 6/11 ENST00000296280.11 NP_624302.1
MASP1NM_001879.6 linkuse as main transcriptc.870G>A p.Trp290Ter stop_gained 6/16 ENST00000337774.10 NP_001870.3
MASP1NM_001031849.3 linkuse as main transcriptc.870G>A p.Trp290Ter stop_gained 6/9 NP_001027019.1
MASP1NR_033519.2 linkuse as main transcriptn.743G>A non_coding_transcript_exon_variant 5/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MASP1ENST00000296280.11 linkuse as main transcriptc.870G>A p.Trp290Ter stop_gained 6/111 NM_139125.4 ENSP00000296280 P48740-2
MASP1ENST00000337774.10 linkuse as main transcriptc.870G>A p.Trp290Ter stop_gained 6/161 NM_001879.6 ENSP00000336792 P1P48740-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251436
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000162
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

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 providedliterature onlyOMIMOct 15, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.66
CADD
Pathogenic
39
DANN
Uncertain
1.0
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A;A;A;A;A
Vest4
0.89
GERP RS
5.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763360042; hg19: chr3-186970978; API