dbSNP rs1485692105: METRN:p.Pro19Gln (chr16-715345-C-A) – 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>A(p.Pro19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,189,388 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: not found (cov: 33)

Exomes 𝑓: 0.0000025 ( 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=0.03953162).

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>A	p.Pro19Gln	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>A	p.Pro19Gln	missense	Exon 1 of 4	ENSP00000455068.1	Q9UJH8
METRN	ENST00000936477.1		c.56C>A	p.Pro19Gln	missense	Exon 1 of 4	ENSP00000606536.1
METRN	ENST00000219542.3	TSL:2	c.8C>A	p.Pro3Gln	missense	Exon 1 of 3	ENSP00000219542.3	J3KMW6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000621

AC:

AN:

16098

AF XY:

0.0000988

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000252

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:

0.00

AC:

AN:

28300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3290

European-Non Finnish (NFE)

AF:

0.00000306

AC:

AN:

979702

Other (OTH)

AF:

0.00

AC:

AN:

48040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0051

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.40

M_CAP

Benign

0.0077

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.24

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.65

REVEL

Benign

0.075

Sift

Benign

0.27

Sift4G

Benign

0.60

Polyphen

0.19

Vest4

0.20

MutPred

0.27

Gain of helix (P = 0.0078)

MVP

0.030

MPC

0.24

ClinPred

0.027

GERP RS

-2.2

PromoterAI

0.054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.25

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

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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