Variant chr19-5893047-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001193375.3(NDUFA11):c.557C>T(p.Ala186Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,535,746 control chromosomes in the GnomAD database, including 4,934 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 340 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4594 hom. )

Consequence

NDUFA11
NM_001193375.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.137

Variant links:

Genes affected

ENSG00000267740 (HGNC:):

ENSG00000267740 links:

NDUFA11 (HGNC:20371): (NADH:ubiquinone oxidoreductase subunit A11) This gene encodes a subunit of the membrane-bound mitochondrial complex I. Complex I is composed of numerous subunits and functions as the NADH-ubiquinol reductase of the mitochondrial electron transport chain. Mutations in this gene are associated with severe mitochondrial complex I deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

NDUFA11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018086135).

BP6

Variant 19-5893047-G-A is Benign according to our data. Variant chr19-5893047-G-A is described in ClinVar as [Benign]. Clinvar id is 1241448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA11	NM_001193375.3 linkuse as main transcript	c.557C>T	p.Ala186Val	missense_variant	4/4		NP_001180304.1	Q86Y39-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
ENSG00000267740	ENST00000586349.5 linkuse as main transcript	c.382+3406C>T		intron_variant		2	ENSP00000466639.1	K7EMT4
NDUFA11	ENST00000418389.6 linkuse as main transcript	c.557C>T	p.Ala186Val	missense_variant	4/4	2	ENSP00000389160.1	Q86Y39-2
ENSG00000267740	ENST00000585661.1 linkuse as main transcript	c.307+3406C>T		intron_variant		2	ENSP00000467210.1	K7EP35
ENSG00000267740	ENST00000592091.5 linkuse as main transcript	n.313+3406C>T		intron_variant		2	ENSP00000465499.1	K7EK78

Frequencies

GnomAD3 genomes

AF:

0.0585

AC:

8901

AN:

152172

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0628

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0878

Gnomad OTH

AF:

0.0784

GnomAD3 exomes

AF:

0.0584

AC:

7965

AN:

136420

Hom.:

292

AF XY:

0.0578

AC XY:

4286

AN XY:

74142

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0456

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.000286

Gnomad SAS exome

AF:

0.0206

Gnomad FIN exome

AF:

0.0515

Gnomad NFE exome

AF:

0.0866

Gnomad OTH exome

AF:

0.0810

GnomAD4 exome

AF:

0.0777

AC:

107550

AN:

1383456

Hom.:

4594

Cov.:

AF XY:

0.0763

AC XY:

52059

AN XY:

682588

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.0495

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.000196

Gnomad4 SAS exome

AF:

0.0217

Gnomad4 FIN exome

AF:

0.0548

Gnomad4 NFE exome

AF:

0.0867

Gnomad4 OTH exome

AF:

0.0762

GnomAD4 genome

AF:

0.0585

AC:

8902

AN:

152290

Hom.:

340

Cov.:

AF XY:

0.0548

AC XY:

4082

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.0627

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.0877

Gnomad4 OTH

AF:

0.0776

Alfa

AF:

0.0883

Hom.:

618

Bravo

AF:

0.0593

TwinsUK

AF:

0.0906

AC:

336

ALSPAC

AF:

0.0856

AC:

330

ExAC

AF:

0.0412

AC:

776

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.4

DANN

Uncertain

1.0

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

0.040

REVEL

Benign

0.043

Sift

Pathogenic

0.0

Sift4G

Benign

0.47

Vest4

0.033

MPC

0.20

ClinPred

0.0074

GERP RS

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.080

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