rs1553786749

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139125.4(MASP1):c.59A>G(p.His20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MASP1
NM_139125.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Publications

0 publications found

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]

MASP1 Gene-Disease associations (from GenCC):

3MC syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
3MC syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MASP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16602072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP1	NM_139125.4 link	c.59A>G	p.His20Arg	missense_variant	Exon 2 of 11	ENST00000296280.11	NP_624302.1	P48740-2
MASP1	NM_001879.6 link	c.59A>G	p.His20Arg	missense_variant	Exon 2 of 16	ENST00000337774.10	NP_001870.3	P48740-1
MASP1	NM_001031849.3 link	c.59A>G	p.His20Arg	missense_variant	Exon 2 of 9		NP_001027019.1	P48740-3
MASP1	NR_033519.2 link	n.110+5625A>G		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11 link	c.59A>G	p.His20Arg	missense_variant	Exon 2 of 11	1	NM_139125.4	ENSP00000296280.7		P48740-2
MASP1	ENST00000337774.10 link	c.59A>G	p.His20Arg	missense_variant	Exon 2 of 16	1	NM_001879.6	ENSP00000336792.5		P48740-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Mar 03, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.073

T;.;.;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.78

T;T;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.69

N;N;N;.;.

PhyloP100

2.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.42

T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;.;.

Polyphen

0.13

B;B;B;.;.

Vest4

0.46

MutPred

0.60

Gain of ubiquitination at K16 (P = 0.0688);Gain of ubiquitination at K16 (P = 0.0688);Gain of ubiquitination at K16 (P = 0.0688);.;.;

MVP

0.72

MPC

0.15

ClinPred

0.18

GERP RS

4.1

Varity_R

0.094

gMVP

0.26

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over