3-187236485-C-T

Variant names:

• chr3-187236485-C-T
• rs35384947
• NM_139125.4:c.1386G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_139125.4(MASP1):​c.1386G>A​(p.Pro462Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,614,034 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (52 hom.)
• Consequence: MASP1 NM_139125.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.31
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 3-187236485-C-T is Benign according to our data. Variant chr3-187236485-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 463035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1888/152270) while in subpopulation AFR AF = 0.0437 (1814/41534). AF 95% confidence interval is 0.042. There are 35 homozygotes in GnomAd4. There are 877 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139125.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	NM_139125.4	MANE Select	c.1386G>A	p.Pro462Pro	synonymous	Exon 11 of 11	NP_624302.1
	MASP1	NM_001879.6	MANE Plus Clinical	c.1303+4996G>A		intron	N/A	NP_001870.3
	MASP1	NR_033519.2		n.1259G>A		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	ENST00000296280.11	TSL:1 MANE Select	c.1386G>A	p.Pro462Pro	synonymous	Exon 11 of 11	ENSP00000296280.7
	MASP1	ENST00000392472.6	TSL:1	c.1047G>A	p.Pro349Pro	synonymous	Exon 10 of 10	ENSP00000376264.2
	MASP1	ENST00000337774.10	TSL:1 MANE Plus Clinical	c.1303+4996G>A		intron	N/A	ENSP00000336792.5

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1888 AN: 152152 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00326 AC: 820 AN: 251344 AF XY: 0.00242

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.000994

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00134 AC: 1955 AN: 1461764 Hom.: 52 Cov.: 82 AF XY: 0.00115 AC XY: 837 AN XY: 727196

African (AFR) AF: 0.0463 AC: 1550 AN: 33480

American (AMR) AF: 0.00224 AC: 100 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26134

East Asian (EAS) AF: 0.00118 AC: 47 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111984

Other (OTH) AF: 0.00262 AC: 158 AN: 60390

GnomAD4 genome AF: 0.0124 AC: 1888 AN: 152270 Hom.: 35 Cov.: 33 AF XY: 0.0118 AC XY: 877 AN XY: 74456

African (AFR) AF: 0.0437 AC: 1814 AN: 41534

American (AMR) AF: 0.00314 AC: 48 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00549 Hom.: 12

Bravo AF: 0.0141

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

3MC syndrome 1 Benign:2

Oct 18, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Nov 27, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.020
DANN	Benign	0.54
PhyloP100		-2.3
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs35384947; hg19: chr3-186954273; COSMIC: COSV56220834;