dbSNP rs1442138: MMRN1:p.Thr58Ala (chr4-89895143-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007351.3(MMRN1):c.172A>G(p.Thr58Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 1,613,694 control chromosomes in the GnomAD database, including 3,373 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.079 ( 646 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2727 hom. )

Consequence

MMRN1
NM_007351.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.739

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013822615).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMRN1	NM_007351.3 link	c.172A>G	p.Thr58Ala	missense_variant	Exon 1 of 8	ENST00000264790.7	NP_031377.2	Q13201-1
MMRN1	NM_001371403.1 link	c.172A>G	p.Thr58Ala	missense_variant	Exon 2 of 9		NP_001358332.1
MMRN1	XM_047449831.1 link	c.172A>G	p.Thr58Ala	missense_variant	Exon 2 of 8		XP_047305787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMRN1	ENST00000264790.7 link	c.172A>G	p.Thr58Ala	missense_variant	Exon 1 of 8	1	NM_007351.3	ENSP00000264790.2		Q13201-1
MMRN1	ENST00000394980.5 link	c.172A>G	p.Thr58Ala	missense_variant	Exon 2 of 9	5		ENSP00000378431.1		Q13201-1

Frequencies

GnomAD3 genomes

AF:

0.0794

AC:

12060

AN:

151934

Hom.:

644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.0573

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0373

Gnomad FIN

AF:

0.0405

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0567

Gnomad OTH

AF:

0.0795

GnomAD3 exomes

AF:

0.0526

AC:

13173

AN:

250484

Hom.:

541

AF XY:

0.0511

AC XY:

6913

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0294

Gnomad ASJ exome

AF:

0.0573

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0388

Gnomad FIN exome

AF:

0.0465

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0549

GnomAD4 exome

AF:

0.0571

AC:

83410

AN:

1461642

Hom.:

2727

Cov.:

AF XY:

0.0560

AC XY:

40726

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0327

Gnomad4 ASJ exome

AF:

0.0550

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0380

Gnomad4 FIN exome

AF:

0.0466

Gnomad4 NFE exome

AF:

0.0589

Gnomad4 OTH exome

AF:

0.0602

GnomAD4 genome

AF:

0.0794

AC:

12076

AN:

152052

Hom.:

646

Cov.:

AF XY:

0.0762

AC XY:

5665

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0506

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0373

Gnomad4 FIN

AF:

0.0405

Gnomad4 NFE

AF:

0.0567

Gnomad4 OTH

AF:

0.0791

Alfa

AF:

0.0584

Hom.:

650

Bravo

AF:

0.0851

TwinsUK

AF:

0.0577

AC:

214

ALSPAC

AF:

0.0646

AC:

249

ESP6500AA

AF:

0.145

AC:

638

ESP6500EA

AF:

0.0566

AC:

487

ExAC

AF:

0.0548

AC:

6652

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

EpiCase

AF:

0.0514

EpiControl

AF:

0.0562

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.30

DANN

Benign

0.59

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.30

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.042

Sift

Benign

0.23

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.021

MPC

0.012

ClinPred

0.0080

GERP RS

-8.0

Varity_R

0.023

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over