Genetic Variant NM_005003.3:c.453G>T (chr16-23582302-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005003.3(NDUFAB1):c.453G>T(p.Lys151Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000565 in 1,415,362 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

NDUFAB1
NM_005003.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Publications

0 publications found

Variant links:

Genes affected

NDUFAB1 (HGNC:7694): (NADH:ubiquinone oxidoreductase subunit AB1) Predicted to enable acyl binding activity; acyl carrier activity; and fatty acid binding activity. Involved in mitochondrial respiratory chain complex I assembly and protein lipoylation. Located in mitochondrion and nucleoplasm. Part of mitochondrial respiratory chain complex I. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

NDUFAB1 links:

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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;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005003.3. 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
	NDUFAB1	NM_005003.3	MANE Select	c.453G>T	p.Lys151Asn	missense	Exon 4 of 5	NP_004994.1	O14561

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFAB1	ENST00000007516.8	TSL:1 MANE Select	c.453G>T	p.Lys151Asn	missense	Exon 4 of 5	ENSP00000007516.2	O14561
NDUFAB1	ENST00000570319.5	TSL:1	c.453G>T	p.Lys151Asn	missense	Exon 4 of 4	ENSP00000458770.1	O14561
NDUFAB1	ENST00000882847.1		c.546G>T	p.Lys182Asn	missense	Exon 5 of 6	ENSP00000552906.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

199608

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000565

AC:

AN:

1415362

Hom.:

Cov.:

AF XY:

0.00000713

AC XY:

AN XY:

701572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31680

American (AMR)

AF:

0.00

AC:

AN:

36512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24538

East Asian (EAS)

AF:

0.00

AC:

AN:

38640

South Asian (SAS)

AF:

0.00

AC:

AN:

77944

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00000734

AC:

AN:

1090604

Other (OTH)

AF:

0.00

AC:

AN:

58376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

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

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000836

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

PhyloP100

3.3

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.23

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.97

Vest4

0.78

MutPred

0.44

Loss of methylation at K151 (P = 4e-04)

MVP

0.55

MPC

0.99

ClinPred

0.98

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.92

gMVP

0.85

Mutation Taster

=19/81

disease causing

(source)

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

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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