Variant 3-179618490-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002492.4(NDUFB5):c.418C>T(p.Leu140Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NDUFB5
NM_002492.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.518

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB5	NM_002492.4 linkuse as main transcript	c.418C>T	p.Leu140Phe	missense_variant	5/6	ENST00000259037.8	NP_002483.1	O43674-1
NDUFB5	NM_001199957.2 linkuse as main transcript	c.262C>T	p.Leu88Phe	missense_variant	3/4		NP_001186886.1	O43674-2
NDUFB5	NM_001199958.2 linkuse as main transcript	c.342+1446C>T		intron_variant			NP_001186887.1	O43674A0A087WYD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDUFB5	ENST00000259037.8 linkuse as main transcript	c.418C>T	p.Leu140Phe	missense_variant	5/6	1	NM_002492.4	ENSP00000259037.3	O43674-1
ENSG00000288698	ENST00000680408.1 linkuse as main transcript	n.*47C>T		non_coding_transcript_exon_variant	4/26			ENSP00000506198.1	A0A7P0TAR2
ENSG00000288698	ENST00000680408.1 linkuse as main transcript	n.*47C>T		3_prime_UTR_variant	4/26			ENSP00000506198.1	A0A7P0TAR2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

249632

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1460074

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726302

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000226

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jul 27, 2022

The c.418C>T (p.L140F) alteration is located in exon 5 (coding exon 5) of the NDUFB5 gene. This alteration results from a C to T substitution at nucleotide position 418, causing the leucine (L) at amino acid position 140 to be replaced by a phenylalanine (F). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Pathogenic

3.1

M;.;.

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.33

MutPred

0.64

Loss of disorder (P = 0.1918);.;.;

MVP

0.66

MPC

0.73

ClinPred

0.92

GERP RS

6.0

Varity_R

0.45

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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