chr11-47638996-A-C

Position:

• chr11-47638996-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014342.4(MTCH2):​c.143T>G​(p.Val48Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTCH2 NM_014342.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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]

MTCH2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCH2	NM_014342.4	c.143T>G	p.Val48Gly	missense_variant	2/13	ENST00000302503.8	NP_055157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCH2	ENST00000302503.8	c.143T>G	p.Val48Gly	missense_variant	2/13	1	NM_014342.4	ENSP00000303222.3
MTCH2	ENST00000530428.2	c.143T>G	p.Val48Gly	missense_variant	2/12	5		ENSP00000432043.2
MTCH2	ENST00000533571.2	n.190T>G		non_coding_transcript_exon_variant	2/13	2
MTCH2	ENST00000539759.5	n.130T>G		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.143T>G (p.V48G) alteration is located in exon 2 (coding exon 2) of the MTCH2 gene. This alteration results from a T to G substitution at nucleotide position 143, causing the valine (V) at amino acid position 48 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.97	D;.
Vest4		0.62
MutPred		0.64		Loss of stability (P = 0.1373);Loss of stability (P = 0.1373);
MVP		0.61
MPC		0.66
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.70
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47660548;