6-36970449-G-A

Position:

• chr6-36970449-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001271641.2(MTCH1):​c.979C>T​(p.Pro327Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.27

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCH1	NM_001271641.2	c.979C>T	p.Pro327Ser	missense_variant	10/12	ENST00000373627.10	NP_001258570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCH1	ENST00000373627.10	c.979C>T	p.Pro327Ser	missense_variant	10/12	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

Jun 07, 2023

The c.928C>T (p.P310S) alteration is located in exon 10 (coding exon 10) of the MTCH1 gene. This alteration results from a C to T substitution at nucleotide position 928, causing the proline (P) at amino acid position 310 to be replaced by a serine (S). 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	1.0
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	.;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;T;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	2.0	.;M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.5	D;D;D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.029	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		1.0	D;P;.
Vest4		0.82
MutPred		0.76		.;Gain of catalytic residue at P327 (P = 0.0464);.;
MVP		0.91
MPC		1.1
ClinPred		0.98	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr6-36938225;