chr11-47629441-C-T

Variant names:

• chr11-47629441-C-T
• rs3817334
• NM_014342.4:c.540-395G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317231.2(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_001317231.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 222 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317231.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCH2	NM_014342.4	MANE Select	c.540-395G>A		intron	N/A	NP_055157.1
	MTCH2	NM_001317231.2		c.540-395G>A		intron	N/A	NP_001304160.1
	MTCH2	NM_001317232.2		c.513-395G>A		intron	N/A	NP_001304161.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCH2	ENST00000302503.8	TSL:1 MANE Select	c.540-395G>A		intron	N/A	ENSP00000303222.3
	MTCH2	ENST00000947886.1		c.540-395G>A		intron	N/A	ENSP00000617945.1
	MTCH2	ENST00000864071.1		c.570-395G>A		intron	N/A	ENSP00000534130.1

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

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: 62 AN: 146

European-Non Finnish (NFE) AF: 0.402 AC: 12649 AN: 31428

Other (OTH) AF: 0.406 AC: 1057 AN: 2604

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3817334; hg19: chr11-47650993;