Genetic Variant NDUFA3:n.221T>C (chr19-54103097-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000484103.1(NDUFA3):n.221T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,608,196 control chromosomes in the GnomAD database, including 254,784 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 23745 hom., cov: 30)

Exomes 𝑓: 0.56 ( 231039 hom. )

Consequence

NDUFA3
ENST00000484103.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Publications

27 publications found

Variant links:

Genes affected

NDUFA3 (HGNC:7686): (NADH:ubiquinone oxidoreductase subunit A3) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

NDUFA3 Gene-Disease associations (from GenCC):

Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

NDUFA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA3	NM_004542.4 link	c.11-17T>C		intron_variant	Intron 1 of 3	ENST00000485876.6	NP_004533.1	O95167Q6FGG4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA3	ENST00000485876.6 link	c.11-17T>C		intron_variant	Intron 1 of 3	1	NM_004542.4	ENSP00000418438.1		O95167

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84284

AN:

151602

Hom.:

23734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.531

GnomAD2 exomes

AF:

0.516

AC:

125833

AN:

243980

AF XY:

0.519

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.502

Gnomad EAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.560

AC:

816312

AN:

1456476

Hom.:

231039

Cov.:

AF XY:

0.559

AC XY:

405074

AN XY:

724088

show subpopulations

African (AFR)

AF:

0.609

AC:

20336

AN:

33406

American (AMR)

AF:

0.346

AC:

15266

AN:

44080

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

13253

AN:

25950

East Asian (EAS)

AF:

0.464

AC:

18341

AN:

39514

South Asian (SAS)

AF:

0.490

AC:

41986

AN:

85620

European-Finnish (FIN)

AF:

0.531

AC:

28140

AN:

52990

Middle Eastern (MID)

AF:

0.485

AC:

2795

AN:

5760

European-Non Finnish (NFE)

AF:

0.580

AC:

643137

AN:

1108974

Other (OTH)

AF:

0.549

AC:

33058

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

17140

34280

51421

68561

85701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17632

35264

52896

70528

88160

<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:

0.556

AC:

84334

AN:

151720

Hom.:

23745

Cov.:

AF XY:

0.549

AC XY:

40681

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.600

AC:

24799

AN:

41344

American (AMR)

AF:

0.440

AC:

6702

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

1743

AN:

3470

East Asian (EAS)

AF:

0.474

AC:

2428

AN:

5120

South Asian (SAS)

AF:

0.497

AC:

2392

AN:

4814

European-Finnish (FIN)

AF:

0.526

AC:

5554

AN:

10566

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.574

AC:

38988

AN:

67870

Other (OTH)

AF:

0.530

AC:

1118

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1895

3789

5684

7578

9473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.567

Hom.:

98592

Bravo

AF:

0.551

Asia WGS

AF:

0.497

AC:

1730

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

(source)

DANN

Benign

0.50

PhyloP100

-1.2

PromoterAI

0.0054

Neutral

(source)

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

Computational scores

Splicing

Publications

Other links and lift over