dbSNP rs1064608: MTCH2:p.Pro290Ala (chr11-47618877-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

61 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014342.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MTCH2	NM_014342.4	MANE Select	c.868C>G	p.Pro290Ala	missense	Exon 13 of 13	NP_055157.1
MTCH2	NM_001317231.2		c.868C>G	p.Pro290Ala	missense	Exon 13 of 13	NP_001304160.1
MTCH2	NM_001317232.2		c.841C>G	p.Pro281Ala	missense	Exon 12 of 12	NP_001304161.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MTCH2	ENST00000302503.8	TSL:1 MANE Select	c.868C>G	p.Pro290Ala	missense	Exon 13 of 13	ENSP00000303222.3
MTCH2	ENST00000947886.1		c.982C>G	p.Pro328Ala	missense	Exon 14 of 14	ENSP00000617945.1
MTCH2	ENST00000864071.1		c.898C>G	p.Pro300Ala	missense	Exon 13 of 13	ENSP00000534130.1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

42449

AN:

75770

Hom.:

6961

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.323

AC:

80506

AN:

249444

AF XY:

0.324

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 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

African (AFR)

AF:

0.0922

AC:

2729

AN:

29608

American (AMR)

AF:

0.446

AC:

17169

AN:

38470

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

7715

AN:

23368

East Asian (EAS)

AF:

0.328

AC:

11906

AN:

36310

South Asian (SAS)

AF:

0.354

AC:

23676

AN:

66810

European-Finnish (FIN)

AF:

0.445

AC:

18784

AN:

42196

Middle Eastern (MID)

AF:

0.405

AC:

2003

AN:

4940

European-Non Finnish (NFE)

AF:

0.367

AC:

388359

AN:

1059100

Other (OTH)

AF:

0.355

AC:

19927

AN:

56124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

16445

32890

49334

65779

82224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12246

24492

36738

48984

61230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.423

AC:

3832

AN:

9058

American (AMR)

AF:

0.583

AC:

5583

AN:

9574

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1011

AN:

1796

East Asian (EAS)

AF:

0.532

AC:

1596

AN:

3000

South Asian (SAS)

AF:

0.533

AC:

1402

AN:

2632

European-Finnish (FIN)

AF:

0.565

AC:

3666

AN:

6488

Middle Eastern (MID)

AF:

0.515

AC:

106

AN:

206

European-Non Finnish (NFE)

AF:

0.585

AC:

24050

AN:

41080

Other (OTH)

AF:

0.562

AC:

644

AN:

1146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1469

2937

4406

5874

7343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

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

PhyloP100

6.2

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

Mutation Taster

=60/40

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over