dbSNP rs149112882: MTRF1:p.Arg366Leu (chr13-41226460-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004294.4(MTRF1):c.1097G>T(p.Arg366Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R366H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MTRF1
NM_004294.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

Publications

0 publications found

Variant links:

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]

MTRF1 links:

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

KBTBD6-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0668233).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTRF1	NM_004294.4	MANE Select	c.1097G>T	p.Arg366Leu	missense	Exon 8 of 10	NP_004285.2
MTRF1	NM_001354073.1		c.1097G>T	p.Arg366Leu	missense	Exon 13 of 15	NP_001341002.1	O75570-1
MTRF1	NM_001354074.1		c.1097G>T	p.Arg366Leu	missense	Exon 8 of 10	NP_001341003.1	O75570-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTRF1	ENST00000379480.9	TSL:1 MANE Select	c.1097G>T	p.Arg366Leu	missense	Exon 8 of 10	ENSP00000368793.3	O75570-1
MTRF1	ENST00000948294.1		c.1223G>T	p.Arg408Leu	missense	Exon 10 of 12	ENSP00000618353.1
MTRF1	ENST00000948296.1		c.1223G>T	p.Arg408Leu	missense	Exon 10 of 12	ENSP00000618355.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460594

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

85740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111790

Other (OTH)

AF:

0.0000166

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.39

M_CAP

Benign

0.0069

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

PhyloP100

1.2

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

REVEL

Benign

0.070

Sift

Benign

0.20

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.14

MutPred

0.44

Gain of catalytic residue at R366 (P = 0.0061)

MVP

0.37

MPC

0.16

ClinPred

0.18

GERP RS

3.8

Varity_R

0.085

gMVP

0.37

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over