13-41226459-AC-GT

Variant names:

• chr13-41226459-AC-GT
• NM_004294.4:c.1097_1098delGTinsAC
• MTRF1 p.Arg366His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004294.4(MTRF1):​c.1097_1098delGTinsAC​(p.Arg366His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R366C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTRF1 NM_004294.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

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]

KBTBD6-DT (HGNC:56824): (KBTBD6 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004294.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRF1	NM_004294.4	MANE Select	c.1097_1098delGTinsAC	p.Arg366His	missense	N/A	NP_004285.2
	MTRF1	NM_001354073.1		c.1097_1098delGTinsAC	p.Arg366His	missense	N/A	NP_001341002.1	O75570-1
	MTRF1	NM_001354074.1		c.1097_1098delGTinsAC	p.Arg366His	missense	N/A	NP_001341003.1	O75570-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRF1	ENST00000379480.9	TSL:1 MANE Select	c.1097_1098delGTinsAC	p.Arg366His	missense	N/A	ENSP00000368793.3	O75570-1
	MTRF1	ENST00000948294.1		c.1223_1224delGTinsAC	p.Arg408His	missense	N/A	ENSP00000618353.1
	MTRF1	ENST00000948296.1		c.1223_1224delGTinsAC	p.Arg408His	missense	N/A	ENSP00000618355.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-41800595;