X-47142420-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001135998.3(NDUFB11):c.359G>A(p.Arg120His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,209,942 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000023 ( 0 hom. 7 hem. )

Consequence

NDUFB11
NM_001135998.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.56

Publications

1 publications found

Variant links:

Genes affected

NDUFB11 (HGNC:20372): (NADH:ubiquinone oxidoreductase subunit B11) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is located at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to ubiquinone. Mutations in the human gene are associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency. [provided by RefSeq, Dec 2016]

NDUFB11 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
linear skin defects with multiple congenital anomalies 3
Inheritance: XL Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
mitochondrial complex I deficiency, nuclear type 30
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
linear skin defects with multiple congenital anomalies
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

NDUFB11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB11	NM_001135998.3 link	c.359G>A	p.Arg120His	missense_variant	Exon 3 of 3	ENST00000377811.4	NP_001129470.1	Q9NX14-1
NDUFB11	NM_019056.7 link	c.389G>A	p.Arg130His	missense_variant	Exon 3 of 3		NP_061929.2	Q9NX14-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4 link	c.359G>A	p.Arg120His	missense_variant	Exon 3 of 3	1	NM_001135998.3	ENSP00000367042.3		Q9NX14-1

Frequencies

GnomAD3 genomes

AF:

0.0000626

AC:

AN:

111818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000740

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

183167

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1098124

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26402

American (AMR)

AF:

0.0000284

AC:

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19382

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30204

South Asian (SAS)

AF:

0.000148

AC:

AN:

54130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

842093

Other (OTH)

AF:

0.0000217

AC:

AN:

46090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000626

AC:

AN:

111818

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

33986

show subpopulations

African (AFR)

AF:

0.0000651

AC:

AN:

30724

American (AMR)

AF:

0.0000947

AC:

AN:

10560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3547

South Asian (SAS)

AF:

0.000740

AC:

AN:

2702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6089

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53125

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Linear skin defects with multiple congenital anomalies 1

Uncertain:1

Apr 27, 2019

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Sep 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 130 of the NDUFB11 protein (p.Arg130His). This variant is present in population databases (rs782753177, gnomAD 0.02%). This missense change has been observed in individual(s) with NDUFB11-related conditions (PMID: 34490615). ClinVar contains an entry for this variant (Variation ID: 638355). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.77

D;.

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Pathogenic

3.4

M;.

PhyloP100

3.6

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.47

MutPred

0.78

Loss of MoRF binding (P = 0.0116);.;

MVP

0.94

MPC

1.3

ClinPred

0.91

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

gMVP

0.89

Mutation Taster

=96/4

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.

X-47142420-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over