rs200528860

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_014222.3(NDUFA8):c.164G>T(p.Arg55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NDUFA8
NM_014222.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

Publications

0 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 disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.48122 (below the threshold of 3.09). Trascript score misZ: 0.71331 (below the threshold of 3.09). GenCC associations: The gene is linked to mitochondrial complex I deficiency, nuclear type 37.

BP4

Computational evidence support a benign effect (MetaRNN=0.3997313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014222.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA8	NM_014222.3	MANE Select	c.164G>T	p.Arg55Leu	missense	Exon 2 of 4	NP_055037.1	P51970
	NDUFA8	NM_001318195.2		c.164G>T	p.Arg55Leu	missense	Exon 2 of 4	NP_001305124.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFA8	ENST00000373768.4	TSL:1 MANE Select	c.164G>T	p.Arg55Leu	missense	Exon 2 of 4	ENSP00000362873.3	P51970
NDUFA8	ENST00000942086.1		c.155G>T	p.Arg52Leu	missense	Exon 2 of 4	ENSP00000612145.1
NDUFA8	ENST00000886470.1		c.52-4023G>T		intron	N/A	ENSP00000556529.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.10

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.028

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.2

PhyloP100

2.3

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.25

Sift

Uncertain

0.016

Sift4G

Uncertain

0.020

Polyphen

0.11

Vest4

0.36

MutPred

0.46

Loss of disorder (P = 0.0397)

MVP

0.95

MPC

0.39

ClinPred

0.99

GERP RS

4.5

Varity_R

0.27

gMVP

0.60

Mutation Taster

=77/23

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over