Variant 19-5892943-T-C 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.661A>G(p.Thr221Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,454,928 control chromosomes in the GnomAD database, including 160,519 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14375 hom., cov: 33)

Exomes 𝑓: 0.47 ( 146144 hom. )

Consequence

NDUFA11
NM_001193375.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.217

Variant links:

Genes affected

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.473702E-6).

BP6

Variant 19-5892943-T-C is Benign according to our data. Variant chr19-5892943-T-C is described in ClinVar as [Benign]. Clinvar id is 1182880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-5892943-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA11	NM_001193375.3 linkuse as main transcript	c.661A>G	p.Thr221Ala	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA11	ENST00000418389.6 linkuse as main transcript	c.661A>G	p.Thr221Ala	missense_variant	4/4	2			Q86Y39-2

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64296

AN:

151848

Hom.:

14364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.689

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.488

AC:

39254

AN:

80516

Hom.:

9992

AF XY:

0.487

AC XY:

20357

AN XY:

41762

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.585

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.672

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.457

GnomAD4 exome

AF:

0.470

AC:

612107

AN:

1302962

Hom.:

146144

Cov.:

AF XY:

0.470

AC XY:

297729

AN XY:

633214

show subpopulations

Gnomad4 AFR exome

AF:

0.292

Gnomad4 AMR exome

AF:

0.576

Gnomad4 ASJ exome

AF:

0.386

Gnomad4 EAS exome

AF:

0.717

Gnomad4 SAS exome

AF:

0.480

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.457

GnomAD4 genome

AF:

0.423

AC:

64334

AN:

151966

Hom.:

14375

Cov.:

AF XY:

0.429

AC XY:

31880

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.690

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.455

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.445

Hom.:

11162

Bravo

AF:

0.425

TwinsUK

AF:

0.472

AC:

1751

ALSPAC

AF:

0.482

AC:

1857

ExAC

AF:

0.354

AC:

5582

Asia WGS

AF:

0.525

AC:

1821

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mitochondrial complex 1 deficiency, nuclear type 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.6

DANN

Benign

0.49

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0000025

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.090

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.77

Vest4

0.0070

MPC

0.20

ClinPred

0.014

GERP RS

0.31

gMVP

0.050

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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