Genetic Variant NDUFB10:p.Asp36Glu (chr16-1959732-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004548.3(NDUFB10):c.108C>G(p.Asp36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D36D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

NDUFB10
NM_004548.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0680

Publications

1 publications found

Variant links:

Genes affected

NDUFB10 (HGNC:7696): (NADH:ubiquinone oxidoreductase subunit B10) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 35. [provided by Alliance of Genome Resources, Apr 2022]

NDUFB10 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex 1 deficiency, nuclear type 35
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NDUFB10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41257015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004548.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB10	NM_004548.3	MANE Select	c.108C>G	p.Asp36Glu	missense	Exon 1 of 4	NP_004539.1	A8K761

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFB10	ENST00000268668.11	TSL:1 MANE Select	c.108C>G	p.Asp36Glu	missense	Exon 1 of 4	ENSP00000268668.6	O96000-1
NDUFB10	ENST00000543683.6	TSL:1	c.108C>G	p.Asp36Glu	missense	Exon 1 of 3	ENSP00000445086.2	O96000-2
NDUFB10	ENST00000926882.1		c.108C>G	p.Asp36Glu	missense	Exon 1 of 4	ENSP00000596941.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250020

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.1

PhyloP100

0.068

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.46

MVP

0.29

MPC

0.31

ClinPred

0.96

GERP RS

3.0

PromoterAI

0.0091

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.71

gMVP

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over