Variant 4-89909326-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007351.3(MMRN1):c.674A>G(p.Asp225Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000484 in 1,609,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

MMRN1
NM_007351.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

Variant links:

Genes affected

MMRN1 (HGNC:7178): (multimerin 1) Multimerin is a massive, soluble protein found in platelets and in the endothelium of blood vessels. It is comprised of subunits linked by interchain disulfide bonds to form large, variably sized homomultimers. Multimerin is a factor V/Va-binding protein and may function as a carrier protein for platelet factor V. It may also have functions as an extracellular matrix or adhesive protein. Recently, patients with an unusual autosomal-dominant bleeding disorder (factor V Quebec) were found to have a deficiency of platelet multimerin. [provided by RefSeq, Jul 2008]

MMRN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMRN1	NM_007351.3 linkuse as main transcript	c.674A>G	p.Asp225Gly	missense_variant	2/8	ENST00000264790.7	NP_031377.2	Q13201-1
MMRN1	NM_001371403.1 linkuse as main transcript	c.674A>G	p.Asp225Gly	missense_variant	3/9		NP_001358332.1
MMRN1	XM_047449831.1 linkuse as main transcript	c.674A>G	p.Asp225Gly	missense_variant	3/8		XP_047305787.1
MMRN1	NM_001410735.1 linkuse as main transcript	c.-101A>G		5_prime_UTR_variant	2/8		NP_001397664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMRN1	ENST00000264790.7 linkuse as main transcript	c.674A>G	p.Asp225Gly	missense_variant	2/8	1	NM_007351.3	ENSP00000264790.2	Q13201-1
MMRN1	ENST00000394980.5 linkuse as main transcript	c.674A>G	p.Asp225Gly	missense_variant	3/9	5		ENSP00000378431.1	Q13201-1
MMRN1	ENST00000508372 linkuse as main transcript	c.-101A>G		5_prime_UTR_variant	2/8	2		ENSP00000426461.1	E7EPG1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

249974

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000514

AC:

AN:

1458334

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

725506

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000559

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151590

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74050

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000297

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.674A>G (p.D225G) alteration is located in exon 2 (coding exon 2) of the MMRN1 gene. This alteration results from a A to G substitution at nucleotide position 674, causing the aspartic acid (D) at amino acid position 225 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.45

MutationAssessor

Benign

2.0

M;M

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.41

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;D

Vest4

0.88

MVP

0.78

MPC

0.087

ClinPred

0.46

GERP RS

5.3

Varity_R

0.39

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over