6-36976703-T-C

Position:

• chr6-36976703-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001271641.2(MTCH1):​c.701+496A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 411,408 control chromosomes in the GnomAD database, including 5,608 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 0.17 (2435 hom., cov: 32)
  • Exomes 𝑓: 0.15 (3173 hom.)
• Consequence: MTCH1 NM_001271641.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTCH1	NM_001271641.2	c.701+496A>G		intron_variant		ENST00000373627.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCH1	ENST00000373627.10	c.701+496A>G		intron_variant		1	NM_001271641.2	P4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25726 AN: 152008 Hom.: 2422 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.148 AC: 38494 AN: 259282 Hom.: 3173 AF XY: 0.152 AC XY: 22017 AN XY: 144554

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.0509

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.0828

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.169 AC: 25771 AN: 152126 Hom.: 2435 Cov.: 32 AF XY: 0.168 AC XY: 12505 AN XY: 74390

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0871

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.194

Alfa AF: 0.152 Hom.: 2661

Bravo AF: 0.177

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs9296204; hg19: chr6-36944479;