rs73068950

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000296280.11(MASP1):​c.1552G>T​(p.Val518Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V518I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

MASP1
ENST00000296280.11 missense

Scores

5
10
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MASP1NM_139125.4 linkuse as main transcriptc.1552G>T p.Val518Phe missense_variant 11/11 ENST00000296280.11 NP_624302.1
MASP1NM_001879.6 linkuse as main transcriptc.1303+5162G>T intron_variant ENST00000337774.10 NP_001870.3
MASP1NR_033519.2 linkuse as main transcriptn.1425G>T non_coding_transcript_exon_variant 10/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MASP1ENST00000296280.11 linkuse as main transcriptc.1552G>T p.Val518Phe missense_variant 11/111 NM_139125.4 ENSP00000296280 P48740-2
MASP1ENST00000337774.10 linkuse as main transcriptc.1303+5162G>T intron_variant 1 NM_001879.6 ENSP00000336792 P1P48740-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
82
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
24
DANN
Uncertain
1.0
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Pathogenic
0.49
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Pathogenic
1.1
D
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Pathogenic
0.75
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.018
D;D
Polyphen
0.99
D;D
Vest4
0.86
MutPred
0.64
Gain of glycosylation at Y519 (P = 0.0346);.;
MVP
0.93
MPC
0.64
ClinPred
0.96
D
GERP RS
5.1
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs73068950; hg19: chr3-186954107; API