chr11-47622339-T-A

Variant names:

• chr11-47622339-T-A
• rs3817335
• NM_014342.4:c.825+362A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014342.4. 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.825+362A>T		intron	N/A	NP_055157.1
	MTCH2	NM_001317231.2		c.825+362A>T		intron	N/A	NP_001304160.1
	MTCH2	NM_001317232.2		c.798+362A>T		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.825+362A>T		intron	N/A	ENSP00000303222.3
	MTCH2	ENST00000530428.2	TSL:5	c.798+362A>T		intron	N/A	ENSP00000432043.2
	MTCH2	ENST00000525649.5	TSL:2	n.518+362A>T		intron	N/A

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

African (AFR) AF: 0.164 AC: 6814 AN: 41462

American (AMR) AF: 0.372 AC: 5678 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3466

East Asian (EAS) AF: 0.308 AC: 1591 AN: 5166

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4814

European-Finnish (FIN) AF: 0.347 AC: 3651 AN: 10520

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24058 AN: 67946

Other (OTH) AF: 0.324 AC: 683 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		-0.35
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: rs3817335; hg19: chr11-47643891;