Variant 13-41240402-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004294.4(MTRF1):c.729C>T(p.Ser243Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00894 in 1,613,320 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 85 hom. )

Consequence

MTRF1
NM_004294.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.44

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 13-41240402-G-A is Benign according to our data. Variant chr13-41240402-G-A is described in ClinVar as [Benign]. Clinvar id is 778477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.43 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTRF1	NM_004294.4 linkuse as main transcript	c.729C>T	p.Ser243Ser	synonymous_variant	6/10	ENST00000379480.9	NP_004285.2	O75570-1A0A024RDT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTRF1	ENST00000379480.9 linkuse as main transcript	c.729C>T	p.Ser243Ser	synonymous_variant	6/10	1	NM_004294.4	ENSP00000368793.3		O75570-1
MTRF1	ENST00000379477.5 linkuse as main transcript	c.729C>T	p.Ser243Ser	synonymous_variant	8/12	2		ENSP00000368790.1		O75570-1

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1134

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00715

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00718

AC:

1798

AN:

250288

Hom.:

AF XY:

0.00778

AC XY:

1052

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.00825

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00674

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.00721

GnomAD4 exome

AF:

0.00910

AC:

13291

AN:

1461114

Hom.:

Cov.:

AF XY:

0.00916

AC XY:

6657

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00441

Gnomad4 ASJ exome

AF:

0.00766

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.00650

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00793

GnomAD4 genome

AF:

0.00745

AC:

1134

AN:

152206

Hom.:

Cov.:

AF XY:

0.00680

AC XY:

506

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00714

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00788

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0128

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 02, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over