17-83079886-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004431.3(METRNL):​c.71C>T​(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 145,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

METRNL
NM_001004431.3 missense

Scores

3
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11530951).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
METRNLNM_001004431.3 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 4 ENST00000320095.12 NP_001004431.1 Q641Q3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
METRNLENST00000320095.12 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 4 1 NM_001004431.3 ENSP00000315731.6 Q641Q3-1

Frequencies

GnomAD3 genomes
AF:
0.00000689
AC:
1
AN:
145140
Hom.:
0
Cov.:
32
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:
0.0000153
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
836370
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
387592
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000689
AC:
1
AN:
145140
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
70556
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000153
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.71C>T (p.P24L) alteration is located in exon 1 (coding exon 1) of the METRNL gene. This alteration results from a C to T substitution at nucleotide position 71, causing the proline (P) at amino acid position 24 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.013
T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.44
T
M_CAP
Pathogenic
0.34
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
0.27
N
REVEL
Benign
0.012
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.072
T
Polyphen
0.36
B
Vest4
0.17
MutPred
0.24
Loss of glycosylation at P24 (P = 0.001);
MVP
0.043
MPC
1.4
ClinPred
0.71
D
GERP RS
-0.14
Varity_R
0.098
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1467044606; hg19: chr17-81037762; COSMIC: COSV60761758; COSMIC: COSV60761758; API