3-187250279-C-T

Position:

• chr3-187250279-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_139125.4(MASP1):​c.1062G>A​(p.Thr354Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,613,946 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (19 hom.)
• Consequence: MASP1 NM_139125.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.87

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 3-187250279-C-T is Benign according to our data. Variant chr3-187250279-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 531897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.87 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00401 (611/152312) while in subpopulation AFR AF= 0.00868 (361/41572). AF 95% confidence interval is 0.00795. There are 4 homozygotes in gnomad4. There are 336 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_139125.4	c.1062G>A	p.Thr354Thr	synonymous_variant	8/11	ENST00000296280.11	NP_624302.1
MASP1	NM_001879.6	c.1062G>A	p.Thr354Thr	synonymous_variant	8/16	ENST00000337774.10	NP_001870.3
MASP1	NM_001031849.3	c.1062G>A	p.Thr354Thr	synonymous_variant	8/9		NP_001027019.1
MASP1	NR_033519.2	n.935G>A		non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11	c.1062G>A	p.Thr354Thr	synonymous_variant	8/11	1	NM_139125.4	ENSP00000296280.7
MASP1	ENST00000337774.10	c.1062G>A	p.Thr354Thr	synonymous_variant	8/16	1	NM_001879.6	ENSP00000336792.5

Frequencies

GnomAD3 genomes AF: 0.00394 AC: 599 AN: 152194 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00842

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00242 AC: 609 AN: 251458 Hom.: 9 AF XY: 0.00213 AC XY: 289 AN XY: 135898

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0179

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00111 AC: 1620 AN: 1461634 Hom.: 19 Cov.: 31 AF XY: 0.00105 AC XY: 761 AN XY: 727156

Gnomad4 AFR exome AF: 0.00953

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.000172

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.00401 AC: 611 AN: 152312 Hom.: 4 Cov.: 32 AF XY: 0.00451 AC XY: 336 AN XY: 74484

Gnomad4 AFR AF: 0.00868

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.00316

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

3MC syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

MASP1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	1.6
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs116763673; hg19: chr3-186968067;