Variant 12-106978623-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000240050.9(MTERF2):c.92C>T(p.Ala31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,614,126 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 95 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 89 hom. )

Consequence

MTERF2
ENST00000240050.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0430

Variant links:

Genes affected

MTERF2 (HGNC:30779): (mitochondrial transcription termination factor 2) Enables DNA binding activity. Predicted to be involved in termination of mitochondrial transcription. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MTERF2 links:

TMEM263 (HGNC:28281): (transmembrane protein 263) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM263 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027748346).

BP6

Variant 12-106978623-G-A is Benign according to our data. Variant chr12-106978623-G-A is described in ClinVar as [Benign]. Clinvar id is 776748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF2	NM_001033050.3 linkuse as main transcript	c.92C>T	p.Ala31Val	missense_variant	3/3	ENST00000240050.9	NP_001028222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF2	ENST00000240050.9 linkuse as main transcript	c.92C>T	p.Ala31Val	missense_variant	3/3	1	NM_001033050.3	ENSP00000240050	P1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2866

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00477

AC:

1200

AN:

251426

Hom.:

AF XY:

0.00338

AC XY:

459

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0666

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00185

AC:

2702

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1150

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0670

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.0189

AC:

2874

AN:

152240

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1379

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0657

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00354

Hom.:

Bravo

AF:

0.0215

ESP6500AA

AF:

0.0654

AC:

288

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00613

AC:

744

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.2

DANN

Benign

0.88

DEOGEN2

Benign

0.092

T;T;T;T;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.48

.;.;T;T;T;T

MetaRNN

Benign

0.0028

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.72

N;N;N;N;N;D

REVEL

Benign

0.022

Sift

Benign

0.74

T;T;T;T;T;D

Sift4G

Benign

0.30

T;T;T;.;.;.

Polyphen

0.0010

B;B;B;.;.;.

Vest4

0.047

MVP

0.14

MPC

0.050

ClinPred

0.037

GERP RS

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.17

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