Variant 16-715604-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000568223.7(METRN):c.125G>A(p.Gly42Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,241,916 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: not found (cov: 33)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

METRN
ENST00000568223.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

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:

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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=0.12613219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METRN	NM_024042.4 linkuse as main transcript	c.125G>A	p.Gly42Asp	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 linkuse as main transcript	c.125G>A	p.Gly42Asp	missense_variant	2/4	1	NM_024042.4	ENSP00000455068.1	Q9UJH8
METRN	ENST00000219542.3 linkuse as main transcript	c.77G>A	p.Gly26Asp	missense_variant	2/3	2		ENSP00000219542.3	J3KMW6
METRN	ENST00000570132.1 linkuse as main transcript	n.104+211G>A		intron_variant		3		ENSP00000456647.1	H3BSC8
METRN	ENST00000567076.5 linkuse as main transcript	c.-38G>A		upstream_gene_variant		5		ENSP00000459900.1	I3L2T3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000242

AC:

AN:

1241916

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

609964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000108

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

Cov.:

ExAC

AF:

0.0000196

AC:

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

Dec 19, 2023

The c.125G>A (p.G42D) alteration is located in exon 2 (coding exon 2) of the METRN gene. This alteration results from a G to A substitution at nucleotide position 125, causing the glycine (G) at amino acid position 42 to be replaced by an aspartic acid (D). 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

0.21

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Benign

0.82

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.64

T;T

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.49

N;.

MutationTaster

Benign

0.60

N;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.037

Sift

Benign

0.88

T;T

Sift4G

Benign

0.90

T;T

Polyphen

0.019

B;.

Vest4

0.24

MutPred

0.17

Gain of solvent accessibility (P = 0.039);.;

MVP

0.14

MPC

0.49

ClinPred

0.23

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.077

gMVP

0.55

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