Variant 12-31662268-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000357721.3(ETFBKMT):c.314+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,613,484 control chromosomes in the GnomAD database, including 30 homozygotes. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 28 hom. )

Consequence

ETFBKMT
ENST00000357721.3 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.02

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-31662268-G-A is Benign according to our data. Variant chr12-31662268-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642829.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETFBKMT	NM_001135863.2 linkuse as main transcript	c.314+1G>A		splice_donor_variant		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.314+1G>A		splice_donor_variant		1	NM_001135863.2	ENSP00000350353	P1

Frequencies

GnomAD3 genomes

AF:

0.00391

AC:

595

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00577

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00472

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00438

AC:

1097

AN:

250600

Hom.:

AF XY:

0.00452

AC XY:

613

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.000804

Gnomad AMR exome

AF:

0.00481

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00418

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00456

AC:

6660

AN:

1461220

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

3366

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.000882

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00423

Gnomad4 FIN exome

AF:

0.00897

Gnomad4 NFE exome

AF:

0.00469

Gnomad4 OTH exome

AF:

0.00419

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152264

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00576

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.00472

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00387

Hom.:

Bravo

AF:

0.00341

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00385

AC:

467

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00516

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ETFBKMT: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.98

MutationTaster

Benign

1.0

D;D;D;D;D

GERP RS

4.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.49

Position offset: -1

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