Variant 4-89909281-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000264790.7(MMRN1):c.629G>C(p.Trp210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000942 in 1,592,588 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

MMRN1
ENST00000264790.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MMRN1	NM_007351.3 linkuse as main transcript	c.629G>C	p.Trp210Ser	missense_variant	2/8	ENST00000264790.7	NP_031377.2
MMRN1	NM_001371403.1 linkuse as main transcript	c.629G>C	p.Trp210Ser	missense_variant	3/9		NP_001358332.1
MMRN1	XM_047449831.1 linkuse as main transcript	c.629G>C	p.Trp210Ser	missense_variant	3/8		XP_047305787.1
MMRN1	NM_001410735.1 linkuse as main transcript	c.-146G>C		5_prime_UTR_variant	2/8		NP_001397664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMRN1	ENST00000264790.7 linkuse as main transcript	c.629G>C	p.Trp210Ser	missense_variant	2/8	1	NM_007351.3	ENSP00000264790	P1	Q13201-1
MMRN1	ENST00000394980.5 linkuse as main transcript	c.629G>C	p.Trp210Ser	missense_variant	3/9	5		ENSP00000378431	P1	Q13201-1
MMRN1	ENST00000508372.1 linkuse as main transcript	c.-146G>C		5_prime_UTR_variant	2/8	2		ENSP00000426461

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000763

AC:

AN:

1441280

Hom.:

Cov.:

AF XY:

0.00000838

AC XY:

AN XY:

715744

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000998

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151308

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000592

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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 06, 2022

The c.629G>C (p.W210S) alteration is located in exon 2 (coding exon 2) of the MMRN1 gene. This alteration results from a G to C substitution at nucleotide position 629, causing the tryptophan (W) at amino acid position 210 to be replaced by a serine (S). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;D

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.082

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.4

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-11

D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.047

D;D

Polyphen

1.0

D;D

Vest4

0.85

MutPred

0.81

Gain of disorder (P = 0.0023);Gain of disorder (P = 0.0023);

MVP

0.75

MPC

0.087

ClinPred

1.0

GERP RS

5.3

Varity_R

0.93

gMVP

0.53

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