NM_005005.3:c.24C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005005.3(NDUFB9):c.24C>T(p.Pro8Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,614,228 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 5 hom. )

Consequence

NDUFB9
NM_005005.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.549

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 8-124539210-C-T is Benign according to our data. Variant chr8-124539210-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 138472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.549 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB9	NM_005005.3 link	c.24C>T	p.Pro8Pro	synonymous_variant	Exon 1 of 4	ENST00000276689.8	NP_004996.1	Q9Y6M9
TATDN1	NM_032026.4 link	c.-164G>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.24C>T	p.Pro8Pro	synonymous_variant	Exon 1 of 4	1	NM_005005.3	ENSP00000276689.3		Q9Y6M9
TATDN1	ENST00000276692.11 link	c.-164G>A		upstream_gene_variant		1	NM_032026.4	ENSP00000276692.6		Q6P1N9-1

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

377

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00199

AC:

500

AN:

251332

Hom.:

AF XY:

0.00197

AC XY:

268

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00296

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000831

Gnomad NFE exome

AF:

0.00242

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00255

AC:

3722

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1790

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00323

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00283

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00289

Gnomad4 OTH exome

AF:

0.00283

GnomAD4 genome

AF:

0.00247

AC:

377

AN:

152360

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00301

EpiCase

AF:

0.00256

EpiControl

AF:

0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NDUFB9: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Apr 25, 2014

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. -

Mitochondrial complex 1 deficiency, nuclear type 24

Benign:1

Jan 17, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely 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

-0.56

CADD

Benign

8.1

DANN

Benign

0.86

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