11-47629441-C-T

Position:

• chr11-47629441-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MTCH2	NM_014342.4	c.540-395G>A		intron_variant		ENST00000302503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCH2	ENST00000302503.8	c.540-395G>A		intron_variant		1	NM_014342.4	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55257 AN: 151760 Hom.: 10381 Cov.: 32

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

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.364 AC: 55303 AN: 151876 Hom.: 10395 Cov.: 32 AF XY: 0.364 AC XY: 27008 AN XY: 74216

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.382

Alfa AF: 0.399 Hom.: 15006

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	12
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs3817334; hg19: chr11-47650993;