Variant 12-31667910-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001135863.2(ETFBKMT):c.709G>A(p.Val237Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,614,166 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 3 hom. )

Consequence

ETFBKMT
NM_001135863.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

ETFBKMT (HGNC:28739): (electron transfer flavoprotein subunit beta lysine methyltransferase) Enables heat shock protein binding activity and protein-lysine N-methyltransferase activity. Involved in negative regulation of electron transfer activity; negative regulation of fatty acid beta-oxidation using acyl-CoA dehydrogenase; and peptidyl-lysine trimethylation. Located in mitochondrial matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ETFBKMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007243067).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETFBKMT	NM_001135863.2 linkuse as main transcript	c.709G>A	p.Val237Ile	missense_variant	4/4	ENST00000357721.3	NP_001129335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETFBKMT	ENST00000357721.3 linkuse as main transcript	c.709G>A	p.Val237Ile	missense_variant	4/4	1	NM_001135863.2	ENSP00000350353	P1

Frequencies

GnomAD3 genomes

AF:

0.000894

AC:

136

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000815

AC:

205

AN:

251474

Hom.:

AF XY:

0.000883

AC XY:

120

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00183

AC:

2668

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1266

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00227

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.000893

AC:

136

AN:

152282

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.000994

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.000782

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00178

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

Sep 01, 2021

The c.709G>A (p.V237I) alteration is located in exon 4 (coding exon 3) of the ETFBKMT gene. This alteration results from a G to A substitution at nucleotide position 709, causing the valine (V) at amino acid position 237 to be replaced by an isoleucine (I). 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

0.081

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0062

T;T;T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.70

.;.;.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0072

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.46

N;N;N;N

REVEL

Benign

0.017

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.068

MVP

0.014

MPC

0.023

ClinPred

0.00064

GERP RS

2.6

Varity_R

0.039

gMVP

0.42

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