Genetic Variant MTCH2:c.540-395G>A (chr11-47629441-C-T) – 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.540-395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 206,740 control chromosomes in the GnomAD database, including 14,487 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 0.36 ( 10395 hom., cov: 32)

Exomes 𝑓: 0.37 ( 4092 hom. )

Consequence

MTCH2
NM_014342.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.211

Publications

222 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCH2	NM_014342.4 link	c.540-395G>A		intron_variant	Intron 8 of 12	ENST00000302503.8	NP_055157.1	Q9Y6C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTCH2	ENST00000302503.8 link	c.540-395G>A		intron_variant	Intron 8 of 12	1	NM_014342.4	ENSP00000303222.3		Q9Y6C9

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55257

AN:

151760

Hom.:

10381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.375

GnomAD4 exome

AF:

0.374

AC:

20540

AN:

54864

Hom.:

4092

AF XY:

0.370

AC XY:

10841

AN XY:

29312

show subpopulations

African (AFR)

AF:

0.251

AC:

544

AN:

2168

American (AMR)

AF:

0.415

AC:

1693

AN:

4080

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

460

AN:

1278

East Asian (EAS)

AF:

0.292

AC:

1074

AN:

3678

South Asian (SAS)

AF:

0.297

AC:

2264

AN:

7618

European-Finnish (FIN)

AF:

0.395

AC:

737

AN:

1864

Middle Eastern (MID)

AF:

0.425

AC:

AN:

146

European-Non Finnish (NFE)

AF:

0.402

AC:

12649

AN:

31428

Other (OTH)

AF:

0.406

AC:

1057

AN:

2604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

632

1264

1897

2529

3161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

146

292

438

584

730

<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

AF:

0.364

AC:

55303

AN:

151876

Hom.:

10395

Cov.:

AF XY:

0.364

AC XY:

27008

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.260

AC:

10760

AN:

41358

American (AMR)

AF:

0.424

AC:

6475

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1253

AN:

3466

East Asian (EAS)

AF:

0.309

AC:

1598

AN:

5168

South Asian (SAS)

AF:

0.318

AC:

1534

AN:

4826

European-Finnish (FIN)

AF:

0.389

AC:

4091

AN:

10514

Middle Eastern (MID)

AF:

0.459

AC:

134

AN:

292

European-Non Finnish (NFE)

AF:

0.413

AC:

28053

AN:

67972

Other (OTH)

AF:

0.382

AC:

803

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1815

3630

5445

7260

9075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.392

Hom.:

36681

Bravo

AF:

0.363

Asia WGS

AF:

0.308

AC:

1076

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.21

Mutation Taster

=100/0

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