Variant 16-715757-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024042.4(METRN):c.278A>G(p.Gln93Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000471 in 1,273,192 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: 0.0000045 ( 0 hom. )

Consequence

METRN
NM_024042.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34412652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METRN	NM_024042.4 linkuse as main transcript	c.278A>G	p.Gln93Arg	missense_variant	2/4	ENST00000568223.7	NP_076947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
METRN	ENST00000568223.7 linkuse as main transcript	c.278A>G	p.Gln93Arg	missense_variant	2/4	1	NM_024042.4	ENSP00000455068	P2
METRN	ENST00000219542.3 linkuse as main transcript	c.230A>G	p.Gln77Arg	missense_variant	2/3	2		ENSP00000219542
METRN	ENST00000567076.5 linkuse as main transcript	c.119A>G	p.Gln40Arg	missense_variant	1/4	5		ENSP00000459900
METRN	ENST00000570132.1 linkuse as main transcript	c.105-119A>G		intron_variant, NMD_transcript_variant		3		ENSP00000456647

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151602

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

AF:

0.00000446

AC:

AN:

1121590

Hom.:

Cov.:

AF XY:

0.00000929

AC XY:

AN XY:

538288

show subpopulations

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:

0.00000423

Gnomad4 OTH exome

AF:

0.0000223

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151602

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74058

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.:

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

Jan 20, 2023

The c.278A>G (p.Q93R) alteration is located in exon 2 (coding exon 2) of the METRN gene. This alteration results from a A to G substitution at nucleotide position 278, causing the glutamine (Q) at amino acid position 93 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

Benign

0.14

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.022

T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.54

T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.090

T;T

Polyphen

1.0

D;.

Vest4

0.44

MutPred

0.27

Gain of MoRF binding (P = 0.0198);.;

MVP

0.29

MPC

0.94

ClinPred

0.88

GERP RS

4.1

Varity_R

0.30

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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