6-36975706-C-A

Position:

• chr6-36975706-C-A

Variant summary

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

The NM_001271641.2(MTCH1):​c.713G>T​(p.Ser238Ile) variant causes a missense change. 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: MTCH1 NM_001271641.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.01

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.713G>T	p.Ser238Ile	missense_variant	7/12	ENST00000373627.10	NP_001258570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCH1	ENST00000373627.10	c.713G>T	p.Ser238Ile	missense_variant	7/12	1	NM_001271641.2	ENSP00000362730.5

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

Jan 03, 2024

The c.713G>T (p.S238I) alteration is located in exon 7 (coding exon 7) of the MTCH1 gene. This alteration results from a G to T substitution at nucleotide position 713, causing the serine (S) at amino acid position 238 to be replaced by an isoleucine (I). 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	0.66
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.022	D;D;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.79
MutPred		0.49		Loss of disorder (P = 0.0366);Loss of disorder (P = 0.0366);.;
MVP		0.87
MPC		1.4
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-36943482;