13-41252973-C-T

Variant names:

• chr13-41252973-C-T
• rs2039263846
• NM_004294.4:c.565G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004294.4(MTRF1):​c.565G>A​(p.Val189Met) variant causes a missense change. 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: 32)
• Consequence: MTRF1 NM_004294.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

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.565G>A	p.Val189Met	missense	Exon 4 of 10	NP_004285.2
	MTRF1	NM_001354073.1		c.565G>A	p.Val189Met	missense	Exon 9 of 15	NP_001341002.1	O75570-1
	MTRF1	NM_001354074.1		c.565G>A	p.Val189Met	missense	Exon 4 of 10	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.565G>A	p.Val189Met	missense	Exon 4 of 10	ENSP00000368793.3	O75570-1
	MTRF1	ENST00000239852.10	TSL:1	n.*233G>A		non_coding_transcript_exon	Exon 6 of 7	ENSP00000481161.1	Q8N6Z2
	MTRF1	ENST00000497679.6	TSL:3	n.*228G>A		non_coding_transcript_exon	Exon 5 of 6	ENSP00000484414.1	A0A087X1S1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.68		Gain of catalytic residue at V185 (P = 0.0327)
MVP		0.66
MPC		0.58
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.71
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs2039263846; hg19: chr13-41827109; COSMIC: COSV105004131; COSMIC: COSV105004131;