NM_001086521.2:c.28C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_001086521.2(NDUFAF8):c.28C>T(p.Arg10Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000811 in 1,368,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

NDUFAF8
NM_001086521.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

Publications

1 publications found

Variant links:

Genes affected

NDUFAF8 (HGNC:33551): (NADH:ubiquinone oxidoreductase complex assembly factor 8) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Implicated in nuclear type mitochondrial complex I deficiency 34. [provided by Alliance of Genome Resources, Apr 2022]

NDUFAF8 Gene-Disease associations (from GenCC):

mitochondrial complex I deficiency, nuclear type 34
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NDUFAF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.3948 (below the threshold of 3.09). Trascript score misZ: -1.1983 (below the threshold of 3.09). GenCC associations: The gene is linked to mitochondrial complex I deficiency, nuclear type 34, mitochondrial complex I deficiency, Leigh syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.2358095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001086521.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFAF8	NM_001086521.2	MANE Select	c.28C>T	p.Arg10Cys	missense	Exon 1 of 3	NP_001079990.1	A1L188
NDUFAF8	NM_001353403.1		c.-396C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001340332.1
NDUFAF8	NM_001353402.1		c.28C>T	p.Arg10Cys	missense	Exon 1 of 3	NP_001340331.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFAF8	ENST00000431388.3	TSL:1 MANE Select	c.28C>T	p.Arg10Cys	missense	Exon 1 of 3	ENSP00000400184.2	A1L188
NDUFAF8	ENST00000577158.2	TSL:1	n.87C>T		non_coding_transcript_exon	Exon 1 of 3
NDUFAF8	ENST00000573090.1	TSL:3	n.81C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000128

AC:

AN:

15638

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00223

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000469

AC:

AN:

1215742

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

586084

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

23466

American (AMR)

AF:

0.000206

AC:

AN:

9732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16666

East Asian (EAS)

AF:

0.00

AC:

AN:

27286

South Asian (SAS)

AF:

0.00

AC:

AN:

51096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3358

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

991952

Other (OTH)

AF:

0.000121

AC:

AN:

49682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000354

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41578

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000434

ESP6500AA

AF:

0.00134

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000221

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.24

MetaSVM

Uncertain

-0.27

PhyloP100

4.2

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.63

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.69

MVP

0.17

MPC

0.96

ClinPred

0.32

GERP RS

3.8

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.41

gMVP

0.49

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over