chr11-47642420-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014342.4(MTCH2):c.46A>C(p.Ile16Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,609,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 40)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
MTCH2
NM_014342.4 missense
NM_014342.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 4.07
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31998742).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTCH2 | NM_014342.4 | c.46A>C | p.Ile16Leu | missense_variant | 1/13 | ENST00000302503.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTCH2 | ENST00000302503.8 | c.46A>C | p.Ile16Leu | missense_variant | 1/13 | 1 | NM_014342.4 | P1 | |
MTCH2 | ENST00000530428.2 | c.46A>C | p.Ile16Leu | missense_variant | 1/12 | 5 | |||
MTCH2 | ENST00000533571.2 | n.115A>C | non_coding_transcript_exon_variant | 1/13 | 2 | ||||
MTCH2 | ENST00000539759.5 | n.33A>C | non_coding_transcript_exon_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 40
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GnomAD3 exomes AF: 0.0000130 AC: 3AN: 230586Hom.: 0 AF XY: 0.0000238 AC XY: 3AN XY: 125872
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1457190Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 724842
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 40 AF XY: 0.0000134 AC XY: 1AN XY: 74396
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2023 | The c.46A>C (p.I16L) alteration is located in exon 1 (coding exon 1) of the MTCH2 gene. This alteration results from a A to C substitution at nucleotide position 46, causing the isoleucine (I) at amino acid position 16 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;.
Polyphen
B;.
Vest4
MutPred
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at