dbSNP rs6822: NDUFA8:c.*64G>A (chr9-122144177-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014222.3(NDUFA8):c.*64G>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 0.169 in 1,611,198 control chromosomes in the GnomAD database, including 26,419 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 0.24 ( 5431 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20988 hom. )

Consequence

NDUFA8
NM_014222.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.734

Publications

17 publications found

Variant links:

Genes affected

NDUFA8 (HGNC:7692): (NADH:ubiquinone oxidoreductase subunit A8) The protein encoded by this gene belongs to the complex I 19 kDa subunit family. Mammalian complex I is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It plays an important role in transfering electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

NDUFA8 Gene-Disease associations (from GenCC):

mitochondrial complex I deficiency, nuclear type 37
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NDUFA8 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA8	NM_014222.3 link	c.*64G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000373768.4	NP_055037.1
NDUFA8	NM_001318195.2 link	c.381+3935G>A		intron_variant	Intron 3 of 3		NP_001305124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA8	ENST00000373768.4 link	c.*64G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_014222.3	ENSP00000362873.3

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36730

AN:

152016

Hom.:

5425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.162

AC:

235998

AN:

1459064

Hom.:

20988

Cov.:

AF XY:

0.161

AC XY:

117143

AN XY:

725832

show subpopulations

African (AFR)

AF:

0.413

AC:

13789

AN:

33402

American (AMR)

AF:

0.238

AC:

10636

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

4922

AN:

26112

East Asian (EAS)

AF:

0.174

AC:

6894

AN:

39670

South Asian (SAS)

AF:

0.171

AC:

14692

AN:

85922

European-Finnish (FIN)

AF:

0.214

AC:

11425

AN:

53328

Middle Eastern (MID)

AF:

0.170

AC:

728

AN:

4294

European-Non Finnish (NFE)

AF:

0.146

AC:

162298

AN:

1111554

Other (OTH)

AF:

0.176

AC:

10614

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

10231

20462

30693

40924

51155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5920

11840

17760

23680

29600

<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:

0.242

AC:

36754

AN:

152134

Hom.:

5431

Cov.:

AF XY:

0.241

AC XY:

17941

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.411

AC:

17066

AN:

41482

American (AMR)

AF:

0.240

AC:

3671

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

648

AN:

3470

East Asian (EAS)

AF:

0.185

AC:

957

AN:

5180

South Asian (SAS)

AF:

0.167

AC:

804

AN:

4816

European-Finnish (FIN)

AF:

0.227

AC:

2401

AN:

10572

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10607

AN:

68004

Other (OTH)

AF:

0.209

AC:

442

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1243

2487

3730

4974

6217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.177

Hom.:

5424

Bravo

AF:

0.249

Asia WGS

AF:

0.212

AC:

735

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.1

(source)

DANN

Benign

0.76

PhyloP100

-0.73

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

Computational scores

Splicing

Publications

Other links and lift over