2-239960810-G-A

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.*308C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,296,478 control chromosomes in the GnomAD database, including 15,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1247 hom., cov: 33)

Exomes 𝑓: 0.15 ( 14278 hom. )

Consequence

NDUFA10
NM_004544.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.13

Publications

16 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=-0.95).

BP6

Variant 2-239960810-G-A is Benign according to our data. Variant chr2-239960810-G-A is described in ClinVar as Benign. ClinVar VariationId is 335198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA10	NM_004544.4 link	c.*308C>T		3_prime_UTR_variant	Exon 10 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.*308C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_004544.4	ENSP00000252711.2		O95299-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17985

AN:

152134

Hom.:

1247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.0870

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.137

GnomAD4 exome

AF:

0.154

AC:

176623

AN:

1144228

Hom.:

14278

Cov.:

AF XY:

0.155

AC XY:

85019

AN XY:

549708

show subpopulations

African (AFR)

AF:

0.0377

AC:

941

AN:

24992

American (AMR)

AF:

0.123

AC:

1904

AN:

15448

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

2826

AN:

14376

East Asian (EAS)

AF:

0.0927

AC:

2055

AN:

22160

South Asian (SAS)

AF:

0.162

AC:

9740

AN:

60200

European-Finnish (FIN)

AF:

0.139

AC:

2341

AN:

16876

Middle Eastern (MID)

AF:

0.145

AC:

423

AN:

2920

European-Non Finnish (NFE)

AF:

0.159

AC:

149949

AN:

942650

Other (OTH)

AF:

0.144

AC:

6444

AN:

44606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

9199

18398

27598

36797

45996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6090

12180

18270

24360

30450

<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:

0.118

AC:

17992

AN:

152250

Hom.:

1247

Cov.:

AF XY:

0.120

AC XY:

8960

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0441

AC:

1833

AN:

41554

American (AMR)

AF:

0.123

AC:

1888

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

725

AN:

3472

East Asian (EAS)

AF:

0.0874

AC:

453

AN:

5186

South Asian (SAS)

AF:

0.155

AC:

747

AN:

4826

European-Finnish (FIN)

AF:

0.151

AC:

1602

AN:

10594

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10262

AN:

68004

Other (OTH)

AF:

0.135

AC:

286

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

836

1671

2507

3342

4178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.143

Hom.:

1268

Bravo

AF:

0.113

Asia WGS

AF:

0.0850

AC:

297

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.95

CADD

Benign

0.091

(source)

DANN

Benign

0.55

PhyloP100

-1.1

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