Variant chr4-89909317-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007351.3(MMRN1):c.665T>C(p.Val222Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,326 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MMRN1
NM_007351.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMRN1	NM_007351.3 link	c.665T>C	p.Val222Ala	missense_variant	2/8	ENST00000264790.7	NP_031377.2	Q13201-1
MMRN1	NM_001371403.1 link	c.665T>C	p.Val222Ala	missense_variant	3/9		NP_001358332.1
MMRN1	XM_047449831.1 link	c.665T>C	p.Val222Ala	missense_variant	3/8		XP_047305787.1
MMRN1	NM_001410735.1 link	c.-110T>C		5_prime_UTR_variant	2/8		NP_001397664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMRN1	ENST00000264790.7 link	c.665T>C	p.Val222Ala	missense_variant	2/8	1	NM_007351.3	ENSP00000264790.2	Q13201-1
MMRN1	ENST00000394980.5 link	c.665T>C	p.Val222Ala	missense_variant	3/9	5		ENSP00000378431.1	Q13201-1
MMRN1	ENST00000508372 link	c.-110T>C		5_prime_UTR_variant	2/8	2		ENSP00000426461.1	E7EPG1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249980

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458326

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 09, 2022

The c.665T>C (p.V222A) alteration is located in exon 2 (coding exon 2) of the MMRN1 gene. This alteration results from a T to C substitution at nucleotide position 665, causing the valine (V) at amino acid position 222 to be replaced by an alanine (A). 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

0.19

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.18

Sift

Benign

0.037

D;D

Sift4G

Benign

0.15

T;T

Polyphen

1.0

D;D

Vest4

0.27

MutPred

0.69

Loss of stability (P = 0.0092);Loss of stability (P = 0.0092);

MVP

0.56

MPC

0.014

ClinPred

0.55

GERP RS

5.3

Varity_R

0.24

gMVP

0.26

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