Variant 8-124539326-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein
NDUFB9	NM_005005.3 linkuse as main transcript	c.101+39C>T	intron_variant	ENST00000276689.8	NP_004996.1
NDUFB9	NM_001278645.2 linkuse as main transcript	c.-33+39C>T	intron_variant		NP_001265574.1
NDUFB9	NM_001278646.2 linkuse as main transcript	c.-27+39C>T	intron_variant		NP_001265575.1
NDUFB9	NM_001311168.2 linkuse as main transcript	c.101+39C>T	intron_variant		NP_001298097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB9	ENST00000276689.8 linkuse as main transcript	c.101+39C>T		intron_variant		1	NM_005005.3	ENSP00000276689	P1

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

GnomAD3 exomes

AF:

0.283

AC:

69929

AN:

246854

Hom.:

10905

AF XY:

0.293

AC XY:

39443

AN XY:

134496

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 SAS exome

AF:

0.437

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

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.354

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.268

AC:

40763

AN:

152046

Hom.:

5729

Cov.:

AF XY:

0.276

AC XY:

20484

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.370

Gnomad4 SAS

AF:

0.442

Gnomad4 FIN

AF:

0.357

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.244

Hom.:

4707

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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