Variant 11-47638773-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014342.4(MTCH2):c.205G>A(p.Gly69Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,614,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 45)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MTCH2
NM_014342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

Variant links:

Genes affected

MTCH2 (HGNC:17587): (mitochondrial carrier 2) This gene encodes a member of the SLC25 family of nuclear-encoded transporters that are localized in the inner mitochondrial membrane. Members of this superfamily are involved in many metabolic pathways and cell functions. Genome-wide association studies in human have identified single-nucleotide polymorphisms in several loci associated with obesity. This gene is one such locus, which is highly expressed in white adipose tissue and adipocytes, and thought to play a regulatory role in adipocyte differentiation and biology. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study showed this gene to be an authentic stop codon readthrough target that can produce two isoforms from the same mRNA by use of alternative in-frame translation termination codons. [provided by RefSeq, Dec 2017]

MTCH2 links:

MTCH2 (HGNC:):

MTCH2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.966

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCH2	NM_014342.4 linkuse as main transcript	c.205G>A	p.Gly69Arg	missense_variant	3/13	ENST00000302503.8	NP_055157.1	Q9Y6C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCH2	ENST00000302503.8 linkuse as main transcript	c.205G>A	p.Gly69Arg	missense_variant	3/13	1	NM_014342.4	ENSP00000303222.3		Q9Y6C9

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251366

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000590

AC:

AN:

152420

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74542

show subpopulations

Gnomad4 AFR

AF:

0.000192

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:

0.0000605

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.205G>A (p.G69R) alteration is located in exon 3 (coding exon 3) of the MTCH2 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the glycine (G) at amino acid position 69 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

0.98

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.075

T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

3.7

H;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.2

D;D

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.041

D;.

Polyphen

1.0

D;.

Vest4

0.84

MutPred

0.91

Loss of methylation at R68 (P = 0.0421);Loss of methylation at R68 (P = 0.0421);

MVP

0.94

MPC

0.83

ClinPred

0.99

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.79

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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