Variant rs1064608 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014342.4(MTCH2):c.868C>G(p.Pro290Ala) variant causes a missense change. The variant allele was found at a frequency of 0.363 in 1,356,926 control chromosomes in the GnomAD database, including 85,801 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.56 ( 6973 hom., cov: 16)

Exomes 𝑓: 0.36 ( 85801 hom. )

Failed GnomAD Quality Control

Consequence

MTCH2
NM_014342.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.23

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017271936).

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTCH2	NM_014342.4 linkuse as main transcript	c.868C>G	p.Pro290Ala	missense_variant	13/13	ENST00000302503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCH2	ENST00000302503.8 linkuse as main transcript	c.868C>G	p.Pro290Ala	missense_variant	13/13	1	NM_014342.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

42449

AN:

75770

Hom.:

6961

Cov.:

FAILED QC

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.553

GnomAD3 exomes

AF:

0.323

AC:

80506

AN:

249444

Hom.:

13850

AF XY:

0.324

AC XY:

43745

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.0859

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.351

Gnomad OTH exome

AF:

0.357

GnomAD4 exome

AF:

0.363

AC:

492268

AN:

1356926

Hom.:

85801

Cov.:

AF XY:

0.367

AC XY:

244215

AN XY:

665736

show subpopulations

Gnomad4 AFR exome

AF:

0.0922

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.354

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.560

AC:

42472

AN:

75792

Hom.:

6973

Cov.:

AF XY:

0.559

AC XY:

20847

AN XY:

37282

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.532

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.565

Gnomad4 NFE

AF:

0.585

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.339

Hom.:

6685

Bravo

AF:

0.273

TwinsUK

AF:

0.350

AC:

1297

ALSPAC

AF:

0.353

AC:

1360

ESP6500AA

AF:

0.0970

AC:

427

ESP6500EA

AF:

0.352

AC:

3023

ExAC

AF:

0.318

AC:

38584

Asia WGS

AF:

0.289

AC:

1007

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.97

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.00038

P;P

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.36

Sift

Benign

0.036

Sift4G

Uncertain

0.037

Polyphen

0.98

Vest4

0.52

MPC

0.57

ClinPred

0.010

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over