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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCH2	NM_014342.4 link	c.868C>G	p.Pro290Ala	missense_variant	Exon 13 of 13	ENST00000302503.8	NP_055157.1	Q9Y6C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTCH2	ENST00000302503.8 link	c.868C>G	p.Pro290Ala	missense_variant	Exon 13 of 13	1	NM_014342.4	ENSP00000303222.3		Q9Y6C9

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over