chr11-47626490-G-A

Position:

• chr11-47626490-G-A

Variant summary

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

The NM_014342.4(MTCH2):​c.681+590C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,730 control chromosomes in the GnomAD database, including 6,977 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 0.28 (6977 hom., cov: 30)
• Consequence: MTCH2 NM_014342.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCH2	NM_014342.4	c.681+590C>T		intron_variant		ENST00000302503.8	NP_055157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCH2	ENST00000302503.8	c.681+590C>T		intron_variant		1	NM_014342.4	ENSP00000303222	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42446 AN: 151610 Hom.: 6965 Cov.: 30

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42468 AN: 151730 Hom.: 6977 Cov.: 30 AF XY: 0.281 AC XY: 20835 AN XY: 74148

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.305

Alfa AF: 0.341 Hom.: 9540

Bravo AF: 0.274

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.54

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: rs4752856; hg19: chr11-47648042;