8-124539326-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005005.3(NDUFB9):c.101+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,605,236 control chromosomes in the GnomAD database, including 63,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5729 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58014 hom. )

Consequence

NDUFB9
NM_005005.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.851

Publications

12 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-124539326-C-T is Benign according to our data. Variant chr8-124539326-C-T is described in ClinVar as [Benign]. Clinvar id is 1291363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB9	NM_005005.3 link	c.101+39C>T		intron_variant	Intron 1 of 3	ENST00000276689.8	NP_004996.1	Q9Y6M9
TATDN1	NM_032026.4 link	c.-280G>A		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.101+39C>T		intron_variant	Intron 1 of 3	1	NM_005005.3	ENSP00000276689.3		Q9Y6M9
TATDN1	ENST00000276692.11 link	c.-280G>A		upstream_gene_variant		1	NM_032026.4	ENSP00000276692.6		Q6P1N9-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40763

AN:

151928

Hom.:

5728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.254

GnomAD2 exomes

AF:

0.283

AC:

69929

AN:

246854

AF XY:

0.293

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.353

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.276

AC:

401141

AN:

1453190

Hom.:

58014

Cov.:

AF XY:

0.281

AC XY:

203233

AN XY:

723434

show subpopulations

African (AFR)

AF:

0.271

AC:

9037

AN:

33334

American (AMR)

AF:

0.139

AC:

6230

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7108

AN:

26080

East Asian (EAS)

AF:

0.411

AC:

16286

AN:

39626

South Asian (SAS)

AF:

0.431

AC:

37050

AN:

86058

European-Finnish (FIN)

AF:

0.354

AC:

18844

AN:

53216

Middle Eastern (MID)

AF:

0.324

AC:

1861

AN:

5746

European-Non Finnish (NFE)

AF:

0.260

AC:

287431

AN:

1104398

Other (OTH)

AF:

0.288

AC:

17294

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

15651

31301

46952

62602

78253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.268

AC:

40763

AN:

152046

Hom.:

5729

Cov.:

AF XY:

0.276

AC XY:

20484

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.266

AC:

11027

AN:

41488

American (AMR)

AF:

0.178

AC:

2721

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

956

AN:

3466

East Asian (EAS)

AF:

0.370

AC:

1904

AN:

5150

South Asian (SAS)

AF:

0.442

AC:

2128

AN:

4814

European-Finnish (FIN)

AF:

0.357

AC:

3769

AN:

10572

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17506

AN:

67954

Other (OTH)

AF:

0.252

AC:

533

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1536

3072

4607

6143

7679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.246

Hom.:

6190

Bravo

AF:

0.251

Asia WGS

AF:

0.387

AC:

1343

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

(source)

DANN

Benign

0.94

PhyloP100

-0.85

PromoterAI

-0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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.

8-124539326-C-T

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