11-47631695-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014342.4(MTCH2):āc.386T>Cā(p.Ile129Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Consequence
MTCH2
NM_014342.4 missense
NM_014342.4 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 7.31
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 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.386T>C | p.Ile129Thr | missense_variant | 6/13 | ENST00000302503.8 | NP_055157.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTCH2 | ENST00000302503.8 | c.386T>C | p.Ile129Thr | missense_variant | 6/13 | 1 | NM_014342.4 | ENSP00000303222.3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 30
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
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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 | Jun 18, 2021 | The c.386T>C (p.I129T) alteration is located in exon 6 (coding exon 6) of the MTCH2 gene. This alteration results from a T to C substitution at nucleotide position 386, causing the isoleucine (I) at amino acid position 129 to be replaced by a threonine (T). 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
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Benign
T;.
Polyphen
B;.
Vest4
MutPred
Gain of disorder (P = 0.0172);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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