Genetic Variant NM_007351.3:c.46G>A (chr4-89895017-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007351.3(MMRN1):c.46G>A(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MMRN1
NM_007351.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

MMRN1 links:

ENSG00000301182 (HGNC:58852):

ENSG00000301182 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09324458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007351.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMRN1	NM_007351.3	MANE Select	c.46G>A	p.Gly16Arg	missense	Exon 1 of 8	NP_031377.2
	MMRN1	NM_001371403.1		c.46G>A	p.Gly16Arg	missense	Exon 2 of 9	NP_001358332.1	Q13201-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMRN1	ENST00000264790.7	TSL:1 MANE Select	c.46G>A	p.Gly16Arg	missense	Exon 1 of 8	ENSP00000264790.2	Q13201-1
MMRN1	ENST00000394980.5	TSL:5	c.46G>A	p.Gly16Arg	missense	Exon 2 of 9	ENSP00000378431.1	Q13201-1
MMRN1	ENST00000955234.1		c.46G>A	p.Gly16Arg	missense	Exon 1 of 8	ENSP00000625293.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461482

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111738

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.050

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.64

M_CAP

Benign

0.022

MetaRNN

Benign

0.093

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

2.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.69

REVEL

Benign

0.032

Sift

Benign

0.40

Sift4G

Benign

0.33

Polyphen

0.054

Vest4

0.23

MutPred

0.44

Gain of MoRF binding (P = 0.0081)

MVP

0.50

MPC

0.014

ClinPred

0.10

GERP RS

2.1

PromoterAI

-0.046

Neutral

(source)

Varity_R

0.019

gMVP

0.41

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over