NM_004544.4:c.105A>G

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.105A>G(p.Lys35Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,613,746 control chromosomes in the GnomAD database, including 356,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37377 hom., cov: 31)

Exomes 𝑓: 0.66 ( 318674 hom. )

Consequence

NDUFA10
NM_004544.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.111

Publications

26 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 (BayesDel_noAF=-0.93).

BP6

Variant 2-240022311-T-C is Benign according to our data. Variant chr2-240022311-T-C is described in ClinVar as Benign. ClinVar VariationId is 129685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.111 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA10	NM_004544.4 link	c.105A>G	p.Lys35Lys	synonymous_variant	Exon 2 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.105A>G	p.Lys35Lys	synonymous_variant	Exon 2 of 10	1	NM_004544.4	ENSP00000252711.2		O95299-1

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

105989

AN:

151898

Hom.:

37333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.694

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.762

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.665

GnomAD2 exomes

AF:

0.665

AC:

167260

AN:

251376

AF XY:

0.661

show subpopulations

Gnomad AFR exome

AF:

0.793

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.639

Gnomad EAS exome

AF:

0.781

Gnomad FIN exome

AF:

0.730

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.640

GnomAD4 exome

AF:

0.659

AC:

962856

AN:

1461730

Hom.:

318674

Cov.:

AF XY:

0.655

AC XY:

476389

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.791

AC:

26466

AN:

33480

American (AMR)

AF:

0.635

AC:

28415

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

16669

AN:

26130

East Asian (EAS)

AF:

0.734

AC:

29118

AN:

39686

South Asian (SAS)

AF:

0.581

AC:

50077

AN:

86254

European-Finnish (FIN)

AF:

0.726

AC:

38745

AN:

53404

Middle Eastern (MID)

AF:

0.559

AC:

3227

AN:

5768

European-Non Finnish (NFE)

AF:

0.657

AC:

730308

AN:

1111894

Other (OTH)

AF:

0.660

AC:

39831

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

19030

38059

57089

76118

95148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19158

38316

57474

76632

95790

<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:

0.698

AC:

106092

AN:

152016

Hom.:

37377

Cov.:

AF XY:

0.700

AC XY:

51978

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.795

AC:

32952

AN:

41448

American (AMR)

AF:

0.661

AC:

10105

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

2242

AN:

3466

East Asian (EAS)

AF:

0.762

AC:

3928

AN:

5154

South Asian (SAS)

AF:

0.576

AC:

2774

AN:

4812

European-Finnish (FIN)

AF:

0.734

AC:

7751

AN:

10560

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.649

AC:

44144

AN:

67986

Other (OTH)

AF:

0.663

AC:

1400

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1603

3205

4808

6410

8013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.663

Hom.:

134596

Bravo

AF:

0.697

Asia WGS

AF:

0.663

AC:

2304

AN:

3478

EpiCase

AF:

0.642

EpiControl

AF:

0.647

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.0

(source)

DANN

Benign

0.44

PhyloP100

-0.11

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