dbSNP rs935752801: MTRF1L:p.Glu303Lys (chr6-152991220-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019041.7(MTRF1L):c.907G>A(p.Glu303Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MTRF1L
NM_019041.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Publications

0 publications found

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:

ENSG00000227627 (HGNC:):

ENSG00000227627 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13301423).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019041.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTRF1L	NM_019041.7	MANE Select	c.907G>A	p.Glu303Lys	missense	Exon 6 of 7	NP_061914.3
MTRF1L	NM_001301870.2		c.799G>A	p.Glu267Lys	missense	Exon 6 of 7	NP_001288799.1
MTRF1L	NM_001301871.2		c.481G>A	p.Glu161Lys	missense	Exon 6 of 7	NP_001288800.1	Q9UGC7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTRF1L	ENST00000367233.10	TSL:1 MANE Select	c.907G>A	p.Glu303Lys	missense	Exon 6 of 7	ENSP00000356202.5	Q9UGC7-1
MTRF1L	ENST00000367231.9	TSL:1	c.806-1125G>A		intron	N/A	ENSP00000356200.5	Q9UGC7-2
MTRF1L	ENST00000367230.5	TSL:1	c.698-1125G>A		intron	N/A	ENSP00000356199.1	Q9UGC7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000511

AC:

AN:

195590

AF XY:

0.00000942

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1411386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700200

African (AFR)

AF:

0.00

AC:

AN:

30910

American (AMR)

AF:

0.00

AC:

AN:

34994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24366

East Asian (EAS)

AF:

0.00

AC:

AN:

38328

South Asian (SAS)

AF:

0.00

AC:

AN:

77118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4036

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091562

Other (OTH)

AF:

0.00

AC:

AN:

58168

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.17

Eigen_PC

Benign

0.0036

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.018

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.31

PhyloP100

3.8

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

REVEL

Benign

0.19

Sift

Benign

0.36

Sift4G

Benign

0.31

Polyphen

0.67

Vest4

0.56

MutPred

0.45

Gain of MoRF binding (P = 0.0038)

MVP

0.14

MPC

0.54

ClinPred

0.23

GERP RS

5.2

Varity_R

0.20

gMVP

0.60

Mutation Taster

=65/35

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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