rs7120548

Variant names:

• chr11-47641380-T-C
• rs7120548
• NM_014342.4:c.87+999A>G

Variant summary

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

The NM_014342.4(MTCH2):​c.87+999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,114 control chromosomes in the GnomAD database, including 5,017 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 0.23 (5017 hom., cov: 32)
• Consequence: MTCH2 NM_014342.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 27 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCH2	NM_014342.4	c.87+999A>G		intron_variant	Intron 1 of 12	ENST00000302503.8	NP_055157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTCH2	ENST00000302503.8	c.87+999A>G		intron_variant	Intron 1 of 12	1	NM_014342.4	ENSP00000303222.3
MTCH2	ENST00000530428.2	c.87+999A>G		intron_variant	Intron 1 of 11	5		ENSP00000432043.2
MTCH2	ENST00000533571.2	n.134+1021A>G		intron_variant	Intron 1 of 12	2
MTCH2	ENST00000539759.5	n.74+999A>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34601 AN: 151996 Hom.: 5020 Cov.: 32

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.227 AC: 34590 AN: 152114 Hom.: 5017 Cov.: 32 AF XY: 0.227 AC XY: 16894 AN XY: 74344

African (AFR) AF: 0.0570 AC: 2366 AN: 41538

American (AMR) AF: 0.223 AC: 3398 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1173 AN: 3464

East Asian (EAS) AF: 0.349 AC: 1806 AN: 5170

South Asian (SAS) AF: 0.453 AC: 2181 AN: 4818

European-Finnish (FIN) AF: 0.217 AC: 2297 AN: 10572

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20529 AN: 67968

Other (OTH) AF: 0.276 AC: 585 AN: 2116

Alfa AF: 0.294 Hom.: 5677

Bravo AF: 0.216

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.92
DANN	Benign	0.72
PhyloP100		-0.91
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: rs7120548; hg19: chr11-47662932;