Variant 13-41252956-A-T 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.582T>A(p.Thr194Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,599,398 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 2 hom. )

Consequence

MTRF1
NM_004294.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.112

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=-0.54).

BP6

Variant 13-41252956-A-T is Benign according to our data. Variant chr13-41252956-A-T is described in ClinVar as [Benign]. Clinvar id is 716440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.112 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTRF1	NM_004294.4 linkuse as main transcript	c.582T>A	p.Thr194Thr	synonymous_variant	4/10	ENST00000379480.9	NP_004285.2	O75570-1A0A024RDT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTRF1	ENST00000379480.9 linkuse as main transcript	c.582T>A	p.Thr194Thr	synonymous_variant	4/10	1	NM_004294.4	ENSP00000368793.3	O75570-1
MTRF1	ENST00000497679.6 linkuse as main transcript	n.*245T>A		non_coding_transcript_exon_variant	5/6	3		ENSP00000484414.1	A0A087X1S1
MTRF1	ENST00000497679.6 linkuse as main transcript	n.*245T>A		3_prime_UTR_variant	5/6	3		ENSP00000484414.1	A0A087X1S1

Frequencies

GnomAD3 genomes

AF:

0.00447

AC:

680

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00671

GnomAD3 exomes

AF:

0.00157

AC:

384

AN:

244858

Hom.:

AF XY:

0.00127

AC XY:

168

AN XY:

132080

show subpopulations

Gnomad AFR exome

AF:

0.0145

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00303

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000708

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000455

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.000757

AC:

1095

AN:

1447068

Hom.:

Cov.:

AF XY:

0.000697

AC XY:

502

AN XY:

719982

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.00208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000251

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000306

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00446

AC:

680

AN:

152330

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

323

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00531

Asia WGS

AF:

0.000867

AC:

AN:

3474

EpiCase

AF:

0.000545

EpiControl

AF:

0.000711

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.3

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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