rs1064608

chr11-47618877-G-Cchr11-47618877-G-T

Variant summary

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

The NM_014342.4(MTCH2):c.868C>G(p.Pro290Ala) variant causes a missense change. The variant allele was found at a frequency of 0.363 in 1,356,926 control chromosomes in the GnomAD database, including 85,801 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (6973 hom., cov: 16)
  • Exomes 𝑓: 0.36 (85801 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTCH2 NM_014342.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.23

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 (MetaRNN=0.0017271936).
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTCH2	NM_014342.4	c.868C>G	p.Pro290Ala	missense_variant	13/13	ENST00000302503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCH2	ENST00000302503.8	c.868C>G	p.Pro290Ala	missense_variant	13/13	1	NM_014342.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 42449 AN: 75770 Hom.: 6961 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.553

GnomAD3 exomes AF: 0.323 AC: 80506 AN: 249444 Hom.: 13850 AF XY: 0.324 AC XY: 43745 AN XY: 135056

Gnomad AFR exome AF: 0.0859

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.287

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.357

GnomAD4 exome AF: 0.363 AC: 492268 AN: 1356926 Hom.: 85801 Cov.: 42 AF XY: 0.367 AC XY: 244215 AN XY: 665736

Gnomad4 AFR exome AF: 0.0922

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.560 AC: 42472 AN: 75792 Hom.: 6973 Cov.: 16 AF XY: 0.559 AC XY: 20847 AN XY: 37282

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.562

Alfa AF: 0.339 Hom.: 6685

Bravo AF: 0.273

TwinsUK AF: 0.350 AC: 1297

ALSPAC AF: 0.353 AC: 1360

ESP6500AA AF: 0.0970 AC: 427

ESP6500EA AF: 0.352 AC: 3023

ExAC AF: 0.318 AC: 38584

Asia WGS AF: 0.289 AC: 1007 AN: 3478

EpiCase AF: 0.352

EpiControl AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.97	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.3	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.00038	P;P
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.36
Sift	Benign	0.036	D
Sift4G	Uncertain	0.037	D
Polyphen		0.98	D
Vest4		0.52
MPC		0.57
ClinPred		0.010	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.77

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: rs1064608; hg19: chr11-47640429; COSMIC: COSV56766406; COSMIC: COSV56766406;