3-187219412-T-G

Variant names:

• chr3-187219412-T-G
• rs3852053
• NM_001879.6:c.*659A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001879.6(MASP1):​c.*659A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 153,390 control chromosomes in the GnomAD database, including 20,199 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (19980 hom., cov: 32)
  • Exomes 𝑓: 0.50 (219 hom.)
• Consequence: MASP1 NM_001879.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP1	NM_001879.6	c.*659A>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000337774.10	NP_001870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000337774.10	c.*659A>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_001879.6	ENSP00000336792.5

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73362 AN: 151668 Hom.: 19982 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.498 AC: 799 AN: 1604 Hom.: 219 Cov.: 0 AF XY: 0.512 AC XY: 432 AN XY: 844

African (AFR) AF: 0.200 AC: 2 AN: 10

American (AMR) AF: 0.534 AC: 156 AN: 292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.800 AC: 16 AN: 20

South Asian (SAS) AF: 0.569 AC: 58 AN: 102

European-Finnish (FIN) AF: 0.568 AC: 25 AN: 44

Middle Eastern (MID) AF: 0.553 AC: 21 AN: 38

European-Non Finnish (NFE) AF: 0.475 AC: 487 AN: 1026

Other (OTH) AF: 0.486 AC: 34 AN: 70

GnomAD4 genome AF: 0.483 AC: 73388 AN: 151786 Hom.: 19980 Cov.: 32 AF XY: 0.491 AC XY: 36436 AN XY: 74134

African (AFR) AF: 0.224 AC: 9270 AN: 41466

American (AMR) AF: 0.584 AC: 8901 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4410 AN: 5140

South Asian (SAS) AF: 0.607 AC: 2912 AN: 4798

European-Finnish (FIN) AF: 0.605 AC: 6358 AN: 10502

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38179 AN: 67846

Other (OTH) AF: 0.493 AC: 1040 AN: 2108

Alfa AF: 0.540 Hom.: 38531

Bravo AF: 0.470

Asia WGS AF: 0.661 AC: 2294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.45
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3852053; hg19: chr3-186937200;