rs1442138

chr4-89895143-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.079 (646 hom., cov: 32)
  • Exomes 𝑓: 0.057 (2727 hom.)
• Consequence: MMRN1 NM_007351.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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]

ACMG classification

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/exons	MANE	UniProt
MMRN1	NM_007351.3	c.172A>G	p.Thr58Ala	missense_variant	1/8	ENST00000264790.7
MMRN1	NM_001371403.1	c.172A>G	p.Thr58Ala	missense_variant	2/9
MMRN1	XM_047449831.1	c.172A>G	p.Thr58Ala	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMRN1	ENST00000264790.7	c.172A>G	p.Thr58Ala	missense_variant	1/8	1	NM_007351.3	P1
MMRN1	ENST00000394980.5	c.172A>G	p.Thr58Ala	missense_variant	2/9	5		P1

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12060 AN: 151934 Hom.: 644 Cov.: 32

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

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.: 35 AF XY: 0.0560 AC XY: 40726 AN XY: 727128

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.: 32 AF XY: 0.0762 AC XY: 5665 AN XY: 74338

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	T
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	N
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.28	T
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	T
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

Other links and lift over

dbSNP: rs1442138; hg19: chr4-90816294; COSMIC: COSV53337317;