dbSNP rs200212772: NDUFAB1:p.Leu13Val (chr16-23596254-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005003.3(NDUFAB1):c.37C>G(p.Leu13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,596,952 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 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NDUFAB1
NM_005003.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.1487999).

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.37C>G	p.Leu13Val	missense	Exon 1 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.37C>G	p.Leu13Val	missense	Exon 1 of 5	ENSP00000007516.2	O14561
NDUFAB1	ENST00000570319.5	TSL:1	c.37C>G	p.Leu13Val	missense	Exon 1 of 4	ENSP00000458770.1	O14561
NDUFAB1	ENST00000882847.1		c.37C>G	p.Leu13Val	missense	Exon 1 of 6	ENSP00000552906.1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

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:

0.000478

GnomAD2 exomes

AF:

0.0000143

AC:

AN:

209510

AF XY:

0.0000172

show subpopulations

Gnomad AFR exome

AF:

0.000268

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:

0.0000111

AC:

AN:

1444586

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

717946

show subpopulations

African (AFR)

AF:

0.000495

AC:

AN:

32294

American (AMR)

AF:

0.00

AC:

AN:

42458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25760

East Asian (EAS)

AF:

0.00

AC:

AN:

38342

South Asian (SAS)

AF:

0.00

AC:

AN:

84292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105130

Other (OTH)

AF:

0.00

AC:

AN:

59668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

AF:

0.000164

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41592

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000337

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

Benign

0.078

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.30

Eigen

Benign

0.11

Eigen_PC

Benign

0.018

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.61

M_CAP

Benign

0.0077

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.2

PhyloP100

1.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Benign

0.086

Sift

Benign

0.040

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.41

MVP

0.35

MPC

0.29

ClinPred

0.12

GERP RS

2.8

PromoterAI

-0.097

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.1

Varity_R

0.096

gMVP

0.29

Mutation Taster

=79/21

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over