dbSNP rs138229541: ETFBKMT:c.314+1G>A (chr12-31662268-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001135863.2(ETFBKMT):c.314+1G>A variant causes a splice donor, intron 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
NM_001135863.2 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.02

Publications

8 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2642829.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135863.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETFBKMT	NM_001135863.2	MANE Select	c.314+1G>A	splice_donor intron	N/A	NP_001129335.1	Q8IXQ9
ETFBKMT	NM_001135864.2		c.314+1G>A	splice_donor intron	N/A	NP_001129336.1	Q8IXQ9
ETFBKMT	NM_173802.4		c.314+1G>A	splice_donor intron	N/A	NP_776163.1	Q8IXQ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETFBKMT	ENST00000357721.3	TSL:1 MANE Select	c.314+1G>A	splice_donor intron	N/A	ENSP00000350353.3	Q8IXQ9
ETFBKMT	ENST00000395763.7	TSL:1	c.314+1G>A	splice_donor intron	N/A	ENSP00000379112.3	Q8IXQ9
ETFBKMT	ENST00000538463.5	TSL:1	c.314+1G>A	splice_donor intron	N/A	ENSP00000441421.1	Q8IXQ9

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

GnomAD2 exomes

AF:

0.00438

AC:

1097

AN:

250600

AF XY:

0.00452

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 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

African (AFR)

AF:

0.000867

AC:

AN:

33460

American (AMR)

AF:

0.00512

AC:

229

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.000882

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00423

AC:

365

AN:

86244

European-Finnish (FIN)

AF:

0.00897

AC:

478

AN:

53294

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00469

AC:

5215

AN:

1111664

Other (OTH)

AF:

0.00419

AC:

253

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

329

659

988

1318

1647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152264

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41562

American (AMR)

AF:

0.00576

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0102

AC:

108

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00472

AC:

321

AN:

68030

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00392

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.98

PhyloP100

9.0

GERP RS

4.4

PromoterAI

0.017

Neutral

(source)

Mutation Taster

=38/62

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over