dbSNP rs772489808: NDUFAF2:p.Gln5Glu (chr5-60945268-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174889.5(NDUFAF2):c.13C>G(p.Gln5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NDUFAF2
NM_174889.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.619

Variant links:

Genes affected

NDUFAF2 (HGNC:28086): (NADH:ubiquinone oxidoreductase complex assembly factor 2) NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. This gene encodes a complex I assembly factor. Mutations in this gene cause progressive encephalopathy resulting from mitochondrial complex I deficiency. [provided by RefSeq, Jul 2008]

NDUFAF2 links:

ERCC8 (HGNC:3439): (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

ERCC8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08812952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF2	NM_174889.5 link	c.13C>G	p.Gln5Glu	missense_variant	Exon 1 of 4	ENST00000296597.10	NP_777549.1	Q8N183A0A0S2Z5U1
ERCC8	NM_000082.4 link	c.-260G>C		upstream_gene_variant		ENST00000676185.1	NP_000073.1	Q13216-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF2	ENST00000296597.10 link	c.13C>G	p.Gln5Glu	missense_variant	Exon 1 of 4	1	NM_174889.5	ENSP00000296597.5		Q8N183
ERCC8	ENST00000676185.1 link	c.-260G>C		upstream_gene_variant			NM_000082.4	ENSP00000501614.1		Q13216-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250224

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS 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:

0.00000274

AC:

AN:

1461100

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-0.87

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.090

Sift

Benign

0.37

T;D

Sift4G

Benign

0.34

T;T

Polyphen

0.083

B;.

Vest4

0.27

MutPred

0.34

Loss of catalytic residue at Q5 (P = 0.0081);Loss of catalytic residue at Q5 (P = 0.0081);

MVP

0.69

MPC

0.087

ClinPred

0.048

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over