8-124539144-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005005.3(NDUFB9):c.-43A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,613,300 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 30 hom. )

Consequence

NDUFB9
NM_005005.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.401

Publications

1 publications found

Variant links:

Genes affected

NDUFB9 (HGNC:7704): (NADH:ubiquinone oxidoreductase subunit B9) The protein encoded by this gene is a subunit of the mitochondrial oxidative phosphorylation complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase). Complex I is localized to the inner mitochondrial membrane and functions to dehydrogenate nicotinamide adenine dinucleotide and to shuttle electrons to coenzyme Q. Complex I deficiency is the most common defect found in oxidative phosphorylation disorders and results in a range of conditions, including lethal neonatal disease, hypertrophic cardiomyopathy, liver disease, and adult-onset neurodegenerative disorders. Pseudogenes of this gene are found on chromosomes five, seven and eight. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

NDUFB9 links:

TATDN1 (HGNC:24220): (TatD DNase domain containing 1) Predicted to enable 3'-5'-exodeoxyribonuclease activity. Predicted to be involved in DNA metabolic process and nucleic acid phosphodiester bond hydrolysis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TATDN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 8-124539144-A-G is Benign according to our data. Variant chr8-124539144-A-G is described in ClinVar as [Benign]. Clinvar id is 138470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 30 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB9	NM_005005.3 link	c.-43A>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000276689.8	NP_004996.1	Q9Y6M9
TATDN1	NM_032026.4 link	c.-98T>C		upstream_gene_variant		ENST00000276692.11	NP_114415.1	Q6P1N9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB9	ENST00000276689.8 link	c.-43A>G		5_prime_UTR_variant	Exon 1 of 4	1	NM_005005.3	ENSP00000276689.3		Q9Y6M9
TATDN1	ENST00000276692.11 link	c.-98T>C		upstream_gene_variant		1	NM_032026.4	ENSP00000276692.6		Q6P1N9-1

Frequencies

GnomAD3 genomes

AF:

0.00413

AC:

629

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00529

Gnomad OTH

AF:

0.00862

GnomAD2 exomes

AF:

0.00440

AC:

1103

AN:

250630

AF XY:

0.00433

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00593

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00528

AC:

7712

AN:

1460918

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

3767

AN XY:

726794

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

33464

American (AMR)

AF:

0.00380

AC:

170

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0209

AC:

547

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00206

AC:

178

AN:

86236

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00920

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00566

AC:

6284

AN:

1111178

Other (OTH)

AF:

0.00634

AC:

383

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00413

AC:

629

AN:

152382

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

276

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00264

AC:

110

AN:

41596

American (AMR)

AF:

0.00477

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00529

AC:

360

AN:

68044

Other (OTH)

AF:

0.00853

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00610

Hom.:

Bravo

AF:

0.00449

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 02, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.1

(source)

DANN

Benign

0.63

PhyloP100

-0.40

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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

8-124539144-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over