Variant 16-715840-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024042.4(METRN):c.361T>C(p.Trp121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

METRN
NM_024042.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.986

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 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=0.15524366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METRN	NM_024042.4 link	c.361T>C	p.Trp121Arg	missense_variant	2/4	ENST00000568223.7	NP_076947.1	Q9UJH8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
METRN	ENST00000568223.7 link	c.361T>C	p.Trp121Arg	missense_variant	2/4	1	NM_024042.4	ENSP00000455068.1	Q9UJH8
METRN	ENST00000219542.3 link	c.313T>C	p.Trp105Arg	missense_variant	2/3	2		ENSP00000219542.3	J3KMW6
METRN	ENST00000567076.5 link	c.199T>C	p.Trp67Arg	missense_variant	1/4	5		ENSP00000459900.1	I3L2T3
METRN	ENST00000570132.1 link	n.105-36T>C		intron_variant		3		ENSP00000456647.1	H3BSC8

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151780

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1163858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

561322

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:

0.00000659

AC:

AN:

151780

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74130

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.361T>C (p.W121R) alteration is located in exon 2 (coding exon 2) of the METRN gene. This alteration results from a T to C substitution at nucleotide position 361, causing the tryptophan (W) at amino acid position 121 to be replaced by an arginine (R). 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

Pathogenic

0.84

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.080

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.056

Sift

Benign

0.37

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.089

B;.

Vest4

0.32

MutPred

0.44

Gain of disorder (P = 0.0012);.;

MVP

0.25

MPC

0.76

ClinPred

0.13

GERP RS

2.8

Varity_R

0.36

gMVP

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over