6-36981597-A-G

Position:

• chr6-36981597-A-G

Variant summary

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

The NM_001271641.2(MTCH1):​c.397T>C​(p.Phe133Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTCH1 NM_001271641.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.37

Genes affected

MTCH1 (HGNC:17586): (mitochondrial carrier 1) This gene encodes a member of the mitochondrial carrier family. The encoded protein is localized to the mitochondrion inner membrane and induces apoptosis independent of the proapoptotic proteins Bax and Bak. Pseudogenes on chromosomes 6 and 11 have been identified for this gene. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Oct 2012]

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
MTCH1	NM_001271641.2	c.397T>C	p.Phe133Leu	missense_variant	2/12	ENST00000373627.10	NP_001258570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCH1	ENST00000373627.10	c.397T>C	p.Phe133Leu	missense_variant	2/12	1	NM_001271641.2	ENSP00000362730.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 04, 2024

The c.397T>C (p.F133L) alteration is located in exon 2 (coding exon 2) of the MTCH1 gene. This alteration results from a T to C substitution at nucleotide position 397, causing the phenylalanine (F) at amino acid position 133 to be replaced by a leucine (L). 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	0.97
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M;M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Benign	0.22
Sift	Benign	0.046	D;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.97	D;P;.
Vest4		0.84
MutPred		0.38		Loss of ubiquitination at K137 (P = 0.1091);Loss of ubiquitination at K137 (P = 0.1091);.;
MVP		0.44
MPC		1.2
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.33
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr6-36949373;