X-47142593-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001135998.3(NDUFB11):c.338+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000505 in 1,209,069 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 22 hem. )

Consequence

NDUFB11
NM_001135998.3 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.880

Publications

0 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042089403).

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.338+21C>T		intron_variant	Intron 2 of 2	ENST00000377811.4	NP_001129470.1	Q9NX14-1
NDUFB11	NM_019056.7 link	c.359C>T	p.Ala120Val	missense_variant	Exon 2 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.338+21C>T		intron_variant	Intron 2 of 2	1	NM_001135998.3	ENSP00000367042.3		Q9NX14-1

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111790

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:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000496

AC:

AN:

181457

AF XY:

0.0000454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000736

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000741

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1097279

Hom.:

Cov.:

AF XY:

0.0000607

AC XY:

AN XY:

362687

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26385

American (AMR)

AF:

0.0000570

AC:

AN:

35070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19294

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30199

South Asian (SAS)

AF:

0.0000185

AC:

AN:

53960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.0000570

AC:

AN:

841708

Other (OTH)

AF:

0.0000869

AC:

AN:

46044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111790

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

33980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30716

American (AMR)

AF:

0.00

AC:

AN:

10477

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3586

South Asian (SAS)

AF:

0.00

AC:

AN:

2706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000941

AC:

AN:

53158

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 120 of the NDUFB11 protein (p.Ala120Val). This variant is present in population databases (rs371538526, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with NDUFB11-related conditions. ClinVar contains an entry for this variant (Variation ID: 2051789). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.1

(source)

DANN

Benign

0.49

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.38

M_CAP

Benign

0.0033

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

PhyloP100

-0.88

PrimateAI

Benign

0.37

PROVEAN

Benign

0.010

REVEL

Benign

0.0040

Sift

Benign

0.30

Sift4G

Benign

0.46

Polyphen

0.0030

Vest4

0.15

MVP

0.12

MPC

0.35

ClinPred

0.13

GERP RS

-0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.17

Mutation Taster

=100/0

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-47142593-G-A

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