dbSNP rs771874865: METRNL:p.Pro28Arg (chr17-83079898-C-G) – 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_001004431.3(METRNL):c.83C>G(p.Pro28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000303 in 990,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. P28L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

METRNL
NM_001004431.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0950

Publications

0 publications found

Variant links:

Genes affected

METRNL (HGNC:27584): (meteorin like, glial cell differentiation regulator) Predicted to enable hormone activity. Predicted to be involved in several processes, including brown fat cell differentiation; energy homeostasis; and positive regulation of brown fat cell differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

METRNL links:

Genome browser will be placed here

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=0.11870697).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004431.3. 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
	METRNL	NM_001004431.3	MANE Select	c.83C>G	p.Pro28Arg	missense	Exon 1 of 4	NP_001004431.1	Q641Q3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METRNL	ENST00000320095.12	TSL:1 MANE Select	c.83C>G	p.Pro28Arg	missense	Exon 1 of 4	ENSP00000315731.6	Q641Q3-1

Frequencies

GnomAD3 genomes

AF:

0.00000686

AC:

AN:

145830

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000237

AC:

AN:

844668

Hom.:

Cov.:

AF XY:

0.00000255

AC XY:

AN XY:

391802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15954

American (AMR)

AF:

0.00

AC:

AN:

1442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5488

East Asian (EAS)

AF:

0.00

AC:

AN:

4152

South Asian (SAS)

AF:

0.00

AC:

AN:

17378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1692

European-Non Finnish (NFE)

AF:

0.00000260

AC:

AN:

768728

Other (OTH)

AF:

0.00

AC:

AN:

27974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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

AF:

0.00000686

AC:

AN:

145830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40596

American (AMR)

AF:

0.00

AC:

AN:

14764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3378

East Asian (EAS)

AF:

0.00

AC:

AN:

4940

South Asian (SAS)

AF:

0.00

AC:

AN:

4766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65680

Other (OTH)

AF:

0.00

AC:

AN:

2014

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.22

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

0.095

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.51

REVEL

Benign

0.037

Sift

Uncertain

0.020

Sift4G

Benign

0.27

Polyphen

0.47

Vest4

0.28

MutPred

0.21

Loss of glycosylation at P28 (P = 4e-04)

MVP

0.043

MPC

1.5

ClinPred

0.21

GERP RS

-1.7

PromoterAI

0.0041

Neutral

(source)

Varity_R

0.057

gMVP

0.29

Mutation Taster

=89/11

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