2-240007349-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004544.4(NDUFA10):c.771A>G(p.Gln257Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,582,734 control chromosomes in the GnomAD database, including 130,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11775 hom., cov: 33)

Exomes 𝑓: 0.40 ( 118448 hom. )

Consequence

NDUFA10
NM_004544.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.205

Publications

25 publications found

Variant links:

Genes affected

NDUFA10 (HGNC:7684): (NADH:ubiquinone oxidoreductase subunit A10) The protein encoded by this gene is a component of 42 kDa complex I, the first enzyme complex in the electron transport chain of mitochondria. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. A mutation in this gene was found in an individual with Leigh syndrome. [provided by RefSeq, Apr 2016]

NDUFA10 Gene-Disease associations (from GenCC):

mitochondrial complex I deficiency, nuclear type 22
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
mitochondrial disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

NDUFA10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0091991E-4).

BP6

Variant 2-240007349-T-C is Benign according to our data. Variant chr2-240007349-T-C is described in ClinVar as Benign. ClinVar VariationId is 129686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.205 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA10	NM_004544.4 link	c.771A>G	p.Gln257Gln	synonymous_variant	Exon 7 of 10	ENST00000252711.7	NP_004535.1	O95299-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000252711.7 link	c.771A>G	p.Gln257Gln	synonymous_variant	Exon 7 of 10	1	NM_004544.4	ENSP00000252711.2		O95299-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58804

AN:

151996

Hom.:

11779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.390

GnomAD2 exomes

AF:

0.400

AC:

99544

AN:

248804

AF XY:

0.391

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.446

Gnomad FIN exome

AF:

0.517

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.401

AC:

574194

AN:

1430620

Hom.:

118448

Cov.:

AF XY:

0.397

AC XY:

283092

AN XY:

713180

show subpopulations

African (AFR)

AF:

0.284

AC:

9364

AN:

32978

American (AMR)

AF:

0.468

AC:

20823

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

9315

AN:

25882

East Asian (EAS)

AF:

0.406

AC:

16025

AN:

39504

South Asian (SAS)

AF:

0.244

AC:

20929

AN:

85688

European-Finnish (FIN)

AF:

0.516

AC:

27475

AN:

53224

Middle Eastern (MID)

AF:

0.320

AC:

1834

AN:

5724

European-Non Finnish (NFE)

AF:

0.410

AC:

444697

AN:

1083808

Other (OTH)

AF:

0.400

AC:

23732

AN:

59332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

14709

29418

44126

58835

73544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13452

26904

40356

53808

67260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.387

AC:

58840

AN:

152114

Hom.:

11775

Cov.:

AF XY:

0.391

AC XY:

29059

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.295

AC:

12242

AN:

41506

American (AMR)

AF:

0.449

AC:

6870

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1213

AN:

3472

East Asian (EAS)

AF:

0.445

AC:

2309

AN:

5184

South Asian (SAS)

AF:

0.249

AC:

1201

AN:

4824

European-Finnish (FIN)

AF:

0.518

AC:

5476

AN:

10564

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28243

AN:

67966

Other (OTH)

AF:

0.387

AC:

817

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1842

3684

5527

7369

9211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.401

Hom.:

27686

Bravo

AF:

0.380

TwinsUK

AF:

0.422

AC:

1563

ALSPAC

AF:

0.416

AC:

1602

ESP6500AA

AF:

0.292

AC:

1284

ESP6500EA

AF:

0.407

AC:

3496

ExAC

AF:

0.392

AC:

47595

Asia WGS

AF:

0.346

AC:

1203

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Leigh syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mitochondrial complex I deficiency, nuclear type 22

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

0.10

CADD

Benign

1.2

(source)

DANN

Benign

0.81

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0018

MetaRNN

Benign

0.00010

MetaSVM

Benign

-1.2

PhyloP100

-0.20

PROVEAN

Benign

-0.94

REVEL

Benign

0.16

Sift

Uncertain

0.025

ClinPred

0.0044

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over