chr2-239960704-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004544.4(NDUFA10):c.*414G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,159,702 control chromosomes in the GnomAD database, including 63,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6954 hom., cov: 34)

Exomes 𝑓: 0.33 ( 56687 hom. )

Consequence

NDUFA10
NM_004544.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.03

Publications

18 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-239960704-C-T is Benign according to our data. Variant chr2-239960704-C-T is described in ClinVar as Benign. ClinVar VariationId is 335193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA10	NM_004544.4 link	c.*414G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000252711.7	NP_004535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000252711.7 link	c.*414G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_004544.4	ENSP00000252711.2

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43269

AN:

152074

Hom.:

6952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.276

GnomAD4 exome

AF:

0.331

AC:

333556

AN:

1007510

Hom.:

56687

Cov.:

AF XY:

0.328

AC XY:

156879

AN XY:

478388

show subpopulations

African (AFR)

AF:

0.122

AC:

2560

AN:

21018

American (AMR)

AF:

0.303

AC:

3172

AN:

10476

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

2651

AN:

9358

East Asian (EAS)

AF:

0.377

AC:

4500

AN:

11948

South Asian (SAS)

AF:

0.185

AC:

9154

AN:

49598

European-Finnish (FIN)

AF:

0.438

AC:

3461

AN:

7904

Middle Eastern (MID)

AF:

0.213

AC:

479

AN:

2254

European-Non Finnish (NFE)

AF:

0.345

AC:

296089

AN:

858952

Other (OTH)

AF:

0.319

AC:

11490

AN:

36002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

11729

23459

35188

46918

58647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11678

23356

35034

46712

58390

<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:

0.284

AC:

43274

AN:

152192

Hom.:

6954

Cov.:

AF XY:

0.288

AC XY:

21425

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.138

AC:

5713

AN:

41542

American (AMR)

AF:

0.306

AC:

4677

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

945

AN:

3470

East Asian (EAS)

AF:

0.378

AC:

1956

AN:

5178

South Asian (SAS)

AF:

0.190

AC:

915

AN:

4822

European-Finnish (FIN)

AF:

0.454

AC:

4800

AN:

10578

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.342

AC:

23282

AN:

67996

Other (OTH)

AF:

0.272

AC:

576

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1551

3102

4652

6203

7754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.313

Hom.:

20372

Bravo

AF:

0.269

Asia WGS

AF:

0.259

AC:

900

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 13, 2021

GeneDx

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

- -

Leigh syndrome

Benign:1

Jan 13, 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 13, 2018

Illumina Laboratory Services, Illumina

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

-0.94

CADD

Benign

0.52

(source)

DANN

Benign

0.60

PhyloP100

-2.0

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