Genetic Variant METRN:p.Pro19Arg (chr16-715345-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024042.4(METRN):c.56C>G(p.Pro19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,341,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P19L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

METRN
NM_024042.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.245

Publications

0 publications found

Variant links:

Genes affected

METRN (HGNC:14151): (meteorin, glial cell differentiation regulator) Meteorin regulates glial cell differentiation and promotes the formation of axonal networks during neurogenesis (Nishino et al., 2004 [PubMed 15085178]).[supplied by OMIM, Mar 2008]

METRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029210031).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024042.4. 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
	METRN	NM_024042.4	MANE Select	c.56C>G	p.Pro19Arg	missense	Exon 1 of 4	NP_076947.1	Q9UJH8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
METRN	ENST00000568223.7	TSL:1 MANE Select	c.56C>G	p.Pro19Arg	missense	Exon 1 of 4	ENSP00000455068.1	Q9UJH8
METRN	ENST00000936477.1		c.56C>G	p.Pro19Arg	missense	Exon 1 of 4	ENSP00000606536.1
METRN	ENST00000219542.3	TSL:2	c.8C>G	p.Pro3Arg	missense	Exon 1 of 3	ENSP00000219542.3	J3KMW6

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000954

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000168

AC:

AN:

1189388

Hom.:

Cov.:

AF XY:

0.00000173

AC XY:

AN XY:

579152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23628

American (AMR)

AF:

0.00

AC:

AN:

11264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17078

East Asian (EAS)

AF:

0.00

AC:

AN:

26654

South Asian (SAS)

AF:

0.00

AC:

AN:

51432

European-Finnish (FIN)

AF:

0.0000707

AC:

AN:

28300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

979702

Other (OTH)

AF:

0.00

AC:

AN:

48040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151824

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41394

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000954

AC:

AN:

10480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67910

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.41

M_CAP

Benign

0.0070

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

-0.24

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

1.7

REVEL

Benign

0.047

Sift

Benign

0.27

Sift4G

Benign

0.58

Polyphen

0.0020

Vest4

0.11

MutPred

0.33

Gain of helix (P = 0.005)

MVP

0.040

MPC

0.27

ClinPred

0.083

GERP RS

-2.2

PromoterAI

0.024

Neutral

(source)

Varity_R

0.057

gMVP

0.25

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