rs768566143

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024120.5(NDUFAF5):c.25C>A(p.Arg9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. R9G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NDUFAF5
NM_024120.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.235

Publications

0 publications found

Variant links:

Genes affected

NDUFAF5 (HGNC:15899): (NADH:ubiquinone oxidoreductase complex assembly factor 5) The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. A mutation in this gene results in mitochondrial complex I deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

NDUFAF5 links:

ESF1 (HGNC:15898): (ESF1 nucleolar pre-rRNA processing protein homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ESF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06654975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024120.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFAF5	NM_024120.5	MANE Select	c.25C>A	p.Arg9Ser	missense	Exon 1 of 11	NP_077025.2
NDUFAF5	NM_001039375.3		c.25C>A	p.Arg9Ser	missense	Exon 1 of 10	NP_001034464.1	Q5TEU4-2
NDUFAF5	NM_001352408.2		c.25C>A	p.Arg9Ser	missense	Exon 1 of 9	NP_001339337.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFAF5	ENST00000378106.10	TSL:1 MANE Select	c.25C>A	p.Arg9Ser	missense	Exon 1 of 11	ENSP00000367346.5	Q5TEU4-1
NDUFAF5	ENST00000463598.1	TSL:1	c.25C>A	p.Arg9Ser	missense	Exon 1 of 10	ENSP00000420497.1	Q5TEU4-2
NDUFAF5	ENST00000874783.1		c.25C>A	p.Arg9Ser	missense	Exon 1 of 12	ENSP00000544842.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246860

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

6.85e-7

AC:

AN:

1460526

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.0000224

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111856

Other (OTH)

AF:

0.00

AC:

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.38

CADD

Benign

4.3

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.032

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.45

M_CAP

Benign

0.073

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

PhyloP100

-0.23

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.95

REVEL

Benign

0.093

Sift

Benign

0.14

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.14

MutPred

0.38

Loss of catalytic residue at R9 (P = 0.0381)

MVP

0.29

MPC

0.12

ClinPred

0.072

GERP RS

-3.8

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.17

gMVP

0.62

Mutation Taster

=95/5

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over