chrX-47142593-G-A

Position:

chrX-47142593-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019056.7(NDUFB11):c.359C>T(p.Ala120Val) variant causes a missense 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. 12/16 in silico tools predict 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_019056.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.880

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:

NDUFB11 (HGNC:):

NDUFB11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NDUFB11	NM_001135998.3 linkuse as main transcript	c.338+21C>T		intron_variant		ENST00000377811.4	NP_001129470.1	Q9NX14-1
NDUFB11	NM_019056.7 linkuse as main transcript	c.359C>T	p.Ala120Val	missense_variant	2/3		NP_061929.2	Q9NX14-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4 linkuse as main transcript	c.338+21C>T		intron_variant		1	NM_001135998.3	ENSP00000367042.3		Q9NX14-1

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111790

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

33980

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

GnomAD3 exomes

AF:

0.0000496

AC:

AN:

181457

Hom.:

AF XY:

0.0000454

AC XY:

AN XY:

66075

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000570

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000570

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111790

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

33980

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000941

Gnomad4 OTH

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2023

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over