Variant 6-153002495-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019041.7(MTRF1L):c.191T>C(p.Leu64Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000239 in 1,613,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

MTRF1L
NM_019041.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

Variant links:

Genes affected

MTRF1L (HGNC:21051): (mitochondrial translation release factor 1 like) The protein encoded by this gene plays a role in mitochondrial translation termination, and is thought to be a release factor that is involved in the dissociation of the complete protein from the final tRNA, the ribosome, and the cognate mRNA. This protein acts upon UAA and UAG stop codons, but has no in vitro activity against UGA, which encodes tryptophan in human mitochondrion, or, the mitochondrial non-cognate stop codons, AGA and AGG. This protein shares sequence similarity to bacterial release factors. Pseudogenes of this gene are found on chromosomes 4, 8, and 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

MTRF1L links:

MTRF1L (HGNC:):

MTRF1L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTRF1L	NM_019041.7 linkuse as main transcript	c.191T>C	p.Leu64Ser	missense_variant	1/7	ENST00000367233.10	NP_061914.3	Q9UGC7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTRF1L	ENST00000367233.10 linkuse as main transcript	c.191T>C	p.Leu64Ser	missense_variant	1/7	1	NM_019041.7	ENSP00000356202.5		Q9UGC7-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000200

AC:

AN:

249640

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000400

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000237

AC:

347

AN:

1461200

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

182

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000291

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000256

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000364

Hom.:

Bravo

AF:

0.000230

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.191T>C (p.L64S) alteration is located in exon 1 (coding exon 1) of the MTRF1L gene. This alteration results from a T to C substitution at nucleotide position 191, causing the leucine (L) at amino acid position 64 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.050

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.29

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.74

MVP

0.65

MPC

1.1

ClinPred

0.16

GERP RS

4.9

Varity_R

0.60

gMVP

0.76

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