X-47144528-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001135998.3(NDUFB11):c.152C>A(p.Pro51Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000517 in 1,134,481 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 182 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., 7 hem., cov: 20)

Exomes 𝑓: 0.00053 ( 0 hom. 175 hem. )

Consequence

NDUFB11
NM_001135998.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 4.82

Publications

2 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11926055).

BP6

Variant X-47144528-G-T is Benign according to our data. Variant chrX-47144528-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 445503.

BS2

High Hemizygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB11	NM_001135998.3 link	c.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 3	ENST00000377811.4	NP_001129470.1	Q9NX14-1
NDUFB11	NM_019056.7 link	c.152C>A	p.Pro51Gln	missense_variant	Exon 1 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.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 3	1	NM_001135998.3	ENSP00000367042.3		Q9NX14-1

Frequencies

GnomAD3 genomes

AF:

0.000392

AC:

AN:

99606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000119

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:

0.000704

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000433

AC:

AN:

150239

AF XY:

0.000564

show subpopulations

Gnomad AFR exome

AF:

0.0000936

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000168

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000681

Gnomad NFE exome

AF:

0.000897

Gnomad OTH exome

AF:

0.000289

GnomAD4 exome

AF:

0.000530

AC:

548

AN:

1034875

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

175

AN XY:

325897

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

24741

American (AMR)

AF:

0.0000328

AC:

AN:

30482

Ashkenazi Jewish (ASJ)

AF:

0.000112

AC:

AN:

17808

East Asian (EAS)

AF:

0.00

AC:

AN:

27707

South Asian (SAS)

AF:

0.0000209

AC:

AN:

47812

European-Finnish (FIN)

AF:

0.0000264

AC:

AN:

37846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2905

European-Non Finnish (NFE)

AF:

0.000659

AC:

529

AN:

802944

Other (OTH)

AF:

0.000258

AC:

AN:

42630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.000392

AC:

AN:

99606

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

AN XY:

24334

show subpopulations

African (AFR)

AF:

0.000110

AC:

AN:

27198

American (AMR)

AF:

0.000119

AC:

AN:

8383

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2507

East Asian (EAS)

AF:

0.00

AC:

AN:

3126

South Asian (SAS)

AF:

0.00

AC:

AN:

2184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.000704

AC:

AN:

49681

Other (OTH)

AF:

0.00

AC:

AN:

1291

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000564

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000152

AC:

ExAC

AF:

0.000497

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 19, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 18, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Uncertain:1

Jul 27, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.152C>A (p.P51Q) alteration is located in exon 1 (coding exon 1) of the NDUFB11 gene. This alteration results from a C to A substitution at nucleotide position 152, causing the proline (P) at amino acid position 51 to be replaced by a glutamine (Q). 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

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;.

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.0

M;M

PhyloP100

4.8

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

1.0

D;D

Vest4

0.23

MVP

0.67

MPC

1.1

ClinPred

0.12

GERP RS

4.1

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.24

Mutation Taster

=93/7

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

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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