11-47629441-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014342.4(MTCH2):​c.540-395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 206,740 control chromosomes in the GnomAD database, including 14,487 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 0.36 ( 10395 hom., cov: 32)
Exomes 𝑓: 0.37 ( 4092 hom. )

Consequence

MTCH2
NM_014342.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.211
Variant links:
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTCH2NM_014342.4 linkuse as main transcriptc.540-395G>A intron_variant ENST00000302503.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTCH2ENST00000302503.8 linkuse as main transcriptc.540-395G>A intron_variant 1 NM_014342.4 P1

Frequencies

GnomAD3 genomes
AF:
0.364
AC:
55257
AN:
151760
Hom.:
10381
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.260
Gnomad AMI
AF:
0.662
Gnomad AMR
AF:
0.423
Gnomad ASJ
AF:
0.362
Gnomad EAS
AF:
0.309
Gnomad SAS
AF:
0.319
Gnomad FIN
AF:
0.389
Gnomad MID
AF:
0.446
Gnomad NFE
AF:
0.413
Gnomad OTH
AF:
0.375
GnomAD4 exome
AF:
0.374
AC:
20540
AN:
54864
Hom.:
4092
AF XY:
0.370
AC XY:
10841
AN XY:
29312
show subpopulations
Gnomad4 AFR exome
AF:
0.251
Gnomad4 AMR exome
AF:
0.415
Gnomad4 ASJ exome
AF:
0.360
Gnomad4 EAS exome
AF:
0.292
Gnomad4 SAS exome
AF:
0.297
Gnomad4 FIN exome
AF:
0.395
Gnomad4 NFE exome
AF:
0.402
Gnomad4 OTH exome
AF:
0.406
GnomAD4 genome
AF:
0.364
AC:
55303
AN:
151876
Hom.:
10395
Cov.:
32
AF XY:
0.364
AC XY:
27008
AN XY:
74216
show subpopulations
Gnomad4 AFR
AF:
0.260
Gnomad4 AMR
AF:
0.424
Gnomad4 ASJ
AF:
0.362
Gnomad4 EAS
AF:
0.309
Gnomad4 SAS
AF:
0.318
Gnomad4 FIN
AF:
0.389
Gnomad4 NFE
AF:
0.413
Gnomad4 OTH
AF:
0.382
Alfa
AF:
0.399
Hom.:
15006
Bravo
AF:
0.363
Asia WGS
AF:
0.308
AC:
1076
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
12
DANN
Benign
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3817334; hg19: chr11-47650993; API