Variant 2-241096116-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182501.4(MTERF4):c.1028A>T(p.Glu343Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,611,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MTERF4
NM_182501.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.802

Variant links:

Genes affected

MTERF4 (HGNC:28785): (mitochondrial transcription termination factor 4) Enables rRNA binding activity. Predicted to be involved in rRNA processing and regulation of transcription, DNA-templated. Predicted to act upstream of or within several processes, including mitochondrial transcription; protein targeting to mitochondrion; and ribosome assembly. Located in cytosol and mitochondrion. Part of mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

MTERF4 links:

MTERF4 (HGNC:):

MTERF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09577057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF4	NM_182501.4 linkuse as main transcript	c.1028A>T	p.Glu343Val	missense_variant	4/4	ENST00000391980.7	NP_872307.2	Q7Z6M4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF4	ENST00000391980.7 linkuse as main transcript	c.1028A>T	p.Glu343Val	missense_variant	4/4	1	NM_182501.4	ENSP00000375840.2		Q7Z6M4

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

149246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

249628

Hom.:

AF XY:

0.0000740

AC XY:

AN XY:

135178

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000169

AC:

247

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.000217

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000134

AC:

AN:

149246

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

72938

show subpopulations

Gnomad4 AFR

AF:

0.0000258

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

Aug 07, 2024

The c.1028A>T (p.E343V) alteration is located in exon 4 (coding exon 4) of the MTERF4 gene. This alteration results from a A to T substitution at nucleotide position 1028, causing the glutamic acid (E) at amino acid position 343 to be replaced by a valine (V). 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

Benign

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.24

T;T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.27

T;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-0.67

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.0

.;N;N

REVEL

Benign

0.12

Sift

Benign

0.058

.;T;T

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.97

D;D;.

Vest4

0.17

MVP

0.15

MPC

0.19

ClinPred

0.12

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.17

gMVP

0.14

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