Variant 16-715814-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.335G>A(p.Gly112Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,265,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

METRN
ENST00000568223.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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=0.08481553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METRN	NM_024042.4 linkuse as main transcript	c.335G>A	p.Gly112Asp	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.335G>A	p.Gly112Asp	missense_variant	2/4	1	NM_024042.4	ENSP00000455068.1	Q9UJH8
METRN	ENST00000219542.3 linkuse as main transcript	c.287G>A	p.Gly96Asp	missense_variant	2/3	2		ENSP00000219542.3	J3KMW6
METRN	ENST00000567076.5 linkuse as main transcript	c.173G>A	p.Gly58Asp	missense_variant	1/4	5		ENSP00000459900.1	I3L2T3
METRN	ENST00000570132.1 linkuse as main transcript	n.105-62G>A		intron_variant		3		ENSP00000456647.1	H3BSC8

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151830

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000656

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:

0.00

GnomAD4 exome

AF:

0.00000629

AC:

AN:

1113132

Hom.:

Cov.:

AF XY:

0.00000565

AC XY:

AN XY:

531216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000852

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:

0.0000658

AC:

AN:

151938

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000276

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

Mar 21, 2022

The c.335G>A (p.G112D) 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 335, causing the glycine (G) at amino acid position 112 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

0.097

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.41

N;.

MutationTaster

Benign

0.99

N;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.021

Sift

Benign

0.24

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.10

B;.

Vest4

0.14

MutPred

0.26

Loss of sheet (P = 0.0315);.;

MVP

0.12

MPC

0.44

ClinPred

0.096

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.059

gMVP

0.67

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