3-187236125-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_139125.4(MASP1):c.1746G>A(p.Pro582Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,613,866 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 65 hom. )

Consequence

MASP1
NM_139125.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.20

Publications

6 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-187236125-C-T is Benign according to our data. Variant chr3-187236125-C-T is described in ClinVar as Benign. ClinVar VariationId is 285006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00513 (781/152306) while in subpopulation SAS AF = 0.0197 (95/4824). AF 95% confidence interval is 0.0165. There are 1 homozygotes in GnomAd4. There are 403 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP1	NM_139125.4 link	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 11 of 11	ENST00000296280.11	NP_624302.1	P48740-2
MASP1	NM_001879.6 link	c.1303+5356G>A		intron_variant	Intron 10 of 15	ENST00000337774.10	NP_001870.3	P48740-1
MASP1	NR_033519.2 link	n.1619G>A		non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11 link	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 11 of 11	1	NM_139125.4	ENSP00000296280.7		P48740-2
MASP1	ENST00000337774.10 link	c.1303+5356G>A		intron_variant	Intron 10 of 15	1	NM_001879.6	ENSP00000336792.5		P48740-1

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

782

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00658

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00673

AC:

1683

AN:

250114

AF XY:

0.00728

show subpopulations

Gnomad AFR exome

AF:

0.00165

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.00871

Gnomad FIN exome

AF:

0.000934

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00789

GnomAD4 exome

AF:

0.00733

AC:

10716

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00761

AC XY:

5532

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00179

AC:

AN:

33478

American (AMR)

AF:

0.00313

AC:

140

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00471

AC:

123

AN:

26136

East Asian (EAS)

AF:

0.0171

AC:

680

AN:

39700

South Asian (SAS)

AF:

0.0202

AC:

1745

AN:

86256

European-Finnish (FIN)

AF:

0.00111

AC:

AN:

53108

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00675

AC:

7507

AN:

1111998

Other (OTH)

AF:

0.00652

AC:

394

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

803

1606

2410

3213

4016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

304

608

912

1216

1520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00513

AC:

781

AN:

152306

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

41556

American (AMR)

AF:

0.00392

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

AN:

3472

East Asian (EAS)

AF:

0.0110

AC:

AN:

5182

South Asian (SAS)

AF:

0.0197

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00659

AC:

448

AN:

68032

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00570

Hom.:

Bravo

AF:

0.00524

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00528

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 25, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

3MC syndrome 1

Benign:1

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.79

(source)

DANN

Benign

0.28

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over