rs3817335

Positions:

• chr11-47622339-T-A

Variant summary

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

The NM_014342.4(MTCH2):​c.825+362A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,928 control chromosomes in the GnomAD database, including 7,409 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 0.30 (7409 hom., cov: 32)
• Consequence: MTCH2 NM_014342.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTCH2	NM_014342.4	c.825+362A>T		intron_variant		ENST00000302503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCH2	ENST00000302503.8	c.825+362A>T		intron_variant		1	NM_014342.4	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45547 AN: 151810 Hom.: 7396 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.300 AC: 45584 AN: 151928 Hom.: 7409 Cov.: 32 AF XY: 0.301 AC XY: 22324 AN XY: 74254

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.324

Alfa AF: 0.328 Hom.: 1047

Bravo AF: 0.297

Asia WGS AF: 0.291 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.78

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: rs3817335; hg19: chr11-47643891;