chrX-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 links:

RBM10 (HGNC:9896): (RNA binding motif protein 10) This gene encodes a nuclear protein that belongs to a family proteins that contain an RNA-binding motif. The encoded protein associates with hnRNP proteins and may be involved in regulating alternative splicing. Defects in this gene are the cause of the X-linked recessive disorder, TARP syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

RBM10 Gene-Disease associations (from GenCC):

TARP syndrome
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

RBM10 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135998.3. 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
	NDUFB11	NM_001135998.3	MANE Select	c.152C>A	p.Pro51Gln	missense	Exon 1 of 3	NP_001129470.1	Q9NX14-1
	NDUFB11	NM_019056.7		c.152C>A	p.Pro51Gln	missense	Exon 1 of 3	NP_061929.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFB11	ENST00000377811.4	TSL:1 MANE Select	c.152C>A	p.Pro51Gln	missense	Exon 1 of 3	ENSP00000367042.3	Q9NX14-1
NDUFB11	ENST00000276062.9	TSL:1	c.152C>A	p.Pro51Gln	missense	Exon 1 of 3	ENSP00000276062.9	A0A8J8YU24
RBM10	ENST00000916920.1		c.-1083G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 25	ENSP00000586979.1

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.72

M_CAP

Benign

0.046

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.0

PhyloP100

4.8

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

REVEL

Benign

0.22

Sift

Uncertain

0.017

Sift4G

Uncertain

0.022

Polyphen

1.0

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

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