8-124549788-C-T

Position:

chr8-124549788-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000276689.8(NDUFB9):c.436C>T(p.Pro146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,613,860 control chromosomes in the GnomAD database, including 7,616 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.097 ( 826 hom., cov: 32)

Exomes 𝑓: 0.093 ( 6790 hom. )

Consequence

NDUFB9
ENST00000276689.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.509

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011136234).

BP6

Variant 8-124549788-C-T is Benign according to our data. Variant chr8-124549788-C-T is described in ClinVar as [Benign]. Clinvar id is 138469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NDUFB9	NM_005005.3 linkuse as main transcript	c.436C>T	p.Pro146Ser	missense_variant	4/4	ENST00000276689.8	NP_004996.1
NDUFB9	NM_001311168.2 linkuse as main transcript	c.403C>T	p.Pro135Ser	missense_variant	4/4		NP_001298097.1
NDUFB9	NM_001278646.2 linkuse as main transcript	c.307C>T	p.Pro103Ser	missense_variant	4/4		NP_001265575.1
NDUFB9	NM_001278645.2 linkuse as main transcript	c.268C>T	p.Pro90Ser	missense_variant	4/4		NP_001265574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB9	ENST00000276689.8 linkuse as main transcript	c.436C>T	p.Pro146Ser	missense_variant	4/4	1	NM_005005.3	ENSP00000276689	P1

Frequencies

GnomAD3 genomes

AF:

0.0968

AC:

14710

AN:

152026

Hom.:

825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0835

Gnomad AMR

AF:

0.0618

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0893

Gnomad OTH

AF:

0.0866

GnomAD3 exomes

AF:

0.0920

AC:

23108

AN:

251200

Hom.:

1240

AF XY:

0.0917

AC XY:

12455

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.0413

Gnomad ASJ exome

AF:

0.0538

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.0720

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.0884

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0925

AC:

135268

AN:

1461714

Hom.:

6790

Cov.:

AF XY:

0.0917

AC XY:

66678

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.0428

Gnomad4 ASJ exome

AF:

0.0537

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.0722

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.0952

GnomAD4 genome

AF:

0.0967

AC:

14710

AN:

152146

Hom.:

826

Cov.:

AF XY:

0.0986

AC XY:

7334

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0618

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.0742

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.0893

Gnomad4 OTH

AF:

0.0861

Alfa

AF:

0.0889

Hom.:

1156

Bravo

AF:

0.0913

TwinsUK

AF:

0.0866

AC:

321

ALSPAC

AF:

0.0820

AC:

316

ESP6500AA

AF:

0.103

AC:

452

ESP6500EA

AF:

0.0842

AC:

724

ExAC

AF:

0.0926

AC:

11240

Asia WGS

AF:

0.107

AC:

371

AN:

3478

EpiCase

AF:

0.0841

EpiControl

AF:

0.0833

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 10, 2013

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.2

DANN

Benign

0.92

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.21

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.13

Sift

Benign

0.53

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.0070

B;.

Vest4

0.066

MPC

0.23

ClinPred

0.0081

GERP RS

-0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.26

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