chr13-41246766-C-T

Position:

• chr13-41246766-C-T

Variant summary

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

The NM_004294.4(MTRF1):​c.697+5879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,020 control chromosomes in the GnomAD database, including 31,095 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 0.64 (31095 hom., cov: 32)
• Consequence: MTRF1 NM_004294.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

Genes affected

MTRF1 (HGNC:7469): (mitochondrial translation release factor 1) The protein encoded by this gene was determined by in silico methods to be a mitochondrial protein with similarity to the peptide chain release factors (RFs) discovered in bacteria and yeast. The peptide chain release factors direct the termination of translation in response to the peptide chain termination codons. Initially thought to have a role in the termination of mitochondria protein synthesis, a recent publication found no mitochondrial translation release functionality. Multiple alternatively spliced transcript variants have been suggested by mRNA and EST data; however, their full-length natures are not clear. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTRF1	NM_004294.4	c.697+5879G>A		intron_variant		ENST00000379480.9	NP_004285.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTRF1	ENST00000379480.9	c.697+5879G>A		intron_variant		1	NM_004294.4	ENSP00000368793.3
MTRF1	ENST00000379477.5	c.697+5879G>A		intron_variant		2		ENSP00000368790.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96778 AN: 151902 Hom.: 31081 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.609

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.637 AC: 96829 AN: 152020 Hom.: 31095 Cov.: 32 AF XY: 0.640 AC XY: 47568 AN XY: 74310

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.614

Alfa AF: 0.642 Hom.: 15431

Bravo AF: 0.630

Asia WGS AF: 0.642 AC: 2232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs3794328; hg19: chr13-41820902;