dbSNP rs754481215: MMRN2:p.Lys338Met (chr10-86943771-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024756.3(MMRN2):c.1013A>T(p.Lys338Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,266 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K338R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MMRN2
NM_024756.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

MMRN2 (HGNC:19888): (multimerin 2) This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

MMRN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMRN2	NM_024756.3 link	c.1013A>T	p.Lys338Met	missense_variant	Exon 6 of 7	ENST00000372027.10	NP_079032.2	Q9H8L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMRN2	ENST00000372027.10 link	c.1013A>T	p.Lys338Met	missense_variant	Exon 6 of 7	1	NM_024756.3	ENSP00000361097.4	Q9H8L6
MMRN2	ENST00000610081.5 link	c.*50A>T		downstream_gene_variant		3		ENSP00000477052.1	V9GYS9
MMRN2	ENST00000609457.5 link	c.*101A>T		downstream_gene_variant		3		ENSP00000476378.1	V9GY43
MMRN2	ENST00000488950.1 link	n.*100A>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456266

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111880

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.63

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.7

PhyloP100

4.4

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.54

MutPred

0.30

Loss of ubiquitination at K338 (P = 0.0309);

MVP

0.89

MPC

0.75

ClinPred

0.99

GERP RS

5.1

Varity_R

0.30

gMVP

0.55

Mutation Taster

=72/28

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

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