Genetic Variant METRNL:p.Pro26Leu (chr17-83079892-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004431.3(METRNL):c.77C>T(p.Pro26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 986,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

METRNL
NM_001004431.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.412

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06990376).

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.77C>T	p.Pro26Leu	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.77C>T	p.Pro26Leu	missense	Exon 1 of 4	ENSP00000315731.6	Q641Q3-1

Frequencies

GnomAD3 genomes

AF:

0.0000686

AC:

AN:

145712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000610

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:

0.00

Gnomad OTH

AF:

0.000496

GnomAD4 exome

AF:

0.00000119

AC:

AN:

841202

Hom.:

Cov.:

AF XY:

0.00000256

AC XY:

AN XY:

390018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15884

American (AMR)

AF:

0.000734

AC:

AN:

1362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5418

East Asian (EAS)

AF:

0.00

AC:

AN:

4034

South Asian (SAS)

AF:

0.00

AC:

AN:

17338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

766100

Other (OTH)

AF:

0.00

AC:

AN:

27808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000686

AC:

AN:

145712

Hom.:

Cov.:

AF XY:

0.0000847

AC XY:

AN XY:

70842

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40580

American (AMR)

AF:

0.000610

AC:

AN:

14748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

4958

South Asian (SAS)

AF:

0.00

AC:

AN:

4758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65624

Other (OTH)

AF:

0.000496

AC:

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000140

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

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.012

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.63

PhyloP100

0.41

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.96

REVEL

Benign

0.078

Sift

Benign

0.40

Sift4G

Benign

0.27

Polyphen

0.0010

Vest4

0.22

MutPred

0.22

Loss of glycosylation at P26 (P = 3e-04)

MVP

0.043

MPC

1.4

ClinPred

0.092

GERP RS

1.6

PromoterAI

0.037

Neutral

(source)

Varity_R

0.032

gMVP

0.17

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