Variant 19-5893087-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001193375.3(NDUFA11):c.517T>A(p.Cys173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,536,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

NDUFA11
NM_001193375.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.711

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008442968).

BP6

Variant 19-5893087-A-T is Benign according to our data. Variant chr19-5893087-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-5893087-A-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA11	NM_001193375.3 linkuse as main transcript	c.517T>A	p.Cys173Ser	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+3366T>A		intron_variant		2	ENSP00000466639.1	K7EMT4
NDUFA11	ENST00000418389.6 linkuse as main transcript	c.517T>A	p.Cys173Ser	missense_variant	4/4	2	ENSP00000389160.1	Q86Y39-2
ENSG00000267740	ENST00000585661.1 linkuse as main transcript	c.307+3366T>A		intron_variant		2	ENSP00000467210.1	K7EP35
ENSG00000267740	ENST00000592091.5 linkuse as main transcript	n.313+3366T>A		intron_variant		2	ENSP00000465499.1	K7EK78

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000197

AC:

AN:

136750

Hom.:

AF XY:

0.000202

AC XY:

AN XY:

74340

show subpopulations

Gnomad AFR exome

AF:

0.00140

Gnomad AMR exome

AF:

0.000572

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000560

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.0000838

AC:

116

AN:

1383832

Hom.:

Cov.:

AF XY:

0.0000879

AC XY:

AN XY:

682864

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.000728

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.000345

GnomAD4 genome

AF:

0.000526

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely 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

-0.65

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.0

DANN

Benign

0.48

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.22

M_CAP

Benign

0.0010

MetaRNN

Benign

0.0084

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.53

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.37

Vest4

0.16

MutPred

0.29

Gain of phosphorylation at C173 (P = 0.0081);

MVP

0.043

MPC

0.25

ClinPred

0.0086

GERP RS

-1.6

gMVP

0.045

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