Variant 8-96244035-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000287025.4(MTERF3):c.943A>G(p.Met315Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MTERF3
ENST00000287025.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.64

Variant links:

Genes affected

MTERF3 (HGNC:24258): (mitochondrial transcription termination factor 3) Enables transcription cis-regulatory region binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MTERF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3159838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF3	NM_015942.5 linkuse as main transcript	c.943A>G	p.Met315Val	missense_variant	7/8	ENST00000287025.4	NP_057026.3	Q96E29-1
MTERF3	NM_001286643.1 linkuse as main transcript	c.943A>G	p.Met315Val	missense_variant	7/9		NP_001273572.1	E5RIK9
MTERF3	NM_001362964.1 linkuse as main transcript	c.373A>G	p.Met125Val	missense_variant	7/8		NP_001349893.1
MTERF3	XM_011517054.3 linkuse as main transcript	c.604A>G	p.Met202Val	missense_variant	7/8		XP_011515356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTERF3	ENST00000287025.4 linkuse as main transcript	c.943A>G	p.Met315Val	missense_variant	7/8	1	NM_015942.5	ENSP00000287025.3	Q96E29-1
MTERF3	ENST00000523821.5 linkuse as main transcript	c.943A>G	p.Met315Val	missense_variant	7/9	1		ENSP00000429400.1	E5RIK9
MTERF3	ENST00000522822.5 linkuse as main transcript	c.580A>G	p.Met194Val	missense_variant	5/6	2		ENSP00000430138.1	Q96E29-3
MTERF3	ENST00000524341.5 linkuse as main transcript	c.327+1825A>G		intron_variant		3		ENSP00000429267.1	E5RIY4

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251354

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461498

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000230

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 10, 2022

The c.943A>G (p.M315V) alteration is located in exon 7 (coding exon 6) of the MTERF3 gene. This alteration results from a A to G substitution at nucleotide position 943, causing the methionine (M) at amino acid position 315 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

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

.;.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.030

D;D;D

Sift4G

Benign

0.076

T;T;T

Polyphen

0.87

P;.;P

Vest4

0.66

MVP

0.54

MPC

0.11

ClinPred

0.11

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.43

gMVP

0.48

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