Variant 3-179604901-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002492.4(NDUFB5):c.86T>G(p.Phe29Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,592,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NDUFB5
NM_002492.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0290

Variant links:

Genes affected

NDUFB5 (HGNC:7700): (NADH:ubiquinone oxidoreductase subunit B5) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

NDUFB5 links:

ENSG00000288698 (HGNC:):

ENSG00000288698 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=0.12502044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB5	NM_002492.4 linkuse as main transcript	c.86T>G	p.Phe29Cys	missense_variant	1/6	ENST00000259037.8	NP_002483.1	O43674-1
NDUFB5	NM_001199957.2 linkuse as main transcript	c.86T>G	p.Phe29Cys	missense_variant	1/4		NP_001186886.1	O43674-2
NDUFB5	NM_001199958.2 linkuse as main transcript	c.86T>G	p.Phe29Cys	missense_variant	1/5		NP_001186887.1	O43674A0A087WYD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB5	ENST00000259037.8 linkuse as main transcript	c.86T>G	p.Phe29Cys	missense_variant	1/6	1	NM_002492.4	ENSP00000259037.3		O43674-1
ENSG00000288698	ENST00000680408.1 linkuse as main transcript	n.86T>G		non_coding_transcript_exon_variant	1/26			ENSP00000506198.1		A0A7P0TAR2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1440612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716900

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2024

The c.86T>G (p.F29C) alteration is located in exon 1 (coding exon 1) of the NDUFB5 gene. This alteration results from a T to G substitution at nucleotide position 86, causing the phenylalanine (F) at amino acid position 29 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.055

T;T;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.61

T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;.;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.79

N;.;N;N

REVEL

Benign

0.086

Sift

Benign

0.18

T;.;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0020

B;.;.;.

Vest4

0.23

MutPred

0.54

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.37

MPC

0.26

ClinPred

0.065

GERP RS

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over