Variant 10-100526499-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_005004.4(NDUFB8):c.368C>G(p.Pro123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,611,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

NDUFB8
NM_005004.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.96

Variant links:

Genes affected

NDUFB8 (HGNC:7703): (NADH:ubiquinone oxidoreductase subunit B8) Involved in mitochondrial respiratory chain complex I assembly. Located in endoplasmic reticulum and mitochondrion. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 32. Biomarker of Alzheimer's disease and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

NDUFB8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036386788).

BP6

Variant 10-100526499-G-C is Benign according to our data. Variant chr10-100526499-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2069291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NDUFB8	NM_005004.4 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	4/5	ENST00000299166.9
NDUFB8	NM_001284367.2 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	4/5
NDUFB8	NM_001284368.1 linkuse as main transcript	c.275C>G	p.Pro92Arg	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFB8	ENST00000299166.9 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	4/5	1	NM_005004.4	P1	O95169-1

Frequencies

GnomAD3 genomes

AF:

0.000841

AC:

128

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000170

AC:

AN:

247772

Hom.:

AF XY:

0.0000821

AC XY:

AN XY:

134038

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000747

AC:

109

AN:

1459202

Hom.:

Cov.:

AF XY:

0.0000716

AC XY:

AN XY:

725958

show subpopulations

Gnomad4 AFR exome

AF:

0.00262

Gnomad4 AMR exome

AF:

0.000160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000841

AC:

128

AN:

152284

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.0000888

Hom.:

Bravo

AF:

0.000956

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

NDUFB8-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.5

M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.24

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.56

MVP

0.64

MPC

0.88

ClinPred

0.094

GERP RS

5.4

Varity_R

0.36

gMVP

0.83

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