rs199842745

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_175614.5(NDUFA11):c.311G>T(p.Arg104Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000881 in 1,570,574 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R104C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

NDUFA11
NM_175614.5 missense, splice_region

Scores

Splicing: ADA: 0.6321

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:1

Conservation

PhyloP100: 5.90

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

mitochondrial complex I deficiency, nuclear type 14
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial disease
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

NDUFA11 links:

ENSG00000267740 (HGNC:):

ENSG00000267740 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08424276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175614.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFA11	NM_175614.5	MANE Select	c.311G>T	p.Arg104Leu	missense splice_region	Exon 3 of 4	NP_783313.1	Q86Y39-1
NDUFA11	NM_001193375.3		c.311G>T	p.Arg104Leu	missense splice_region	Exon 3 of 4	NP_001180304.1	Q86Y39-2
NDUFA11	NR_034166.3		n.513G>T		splice_region non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFA11	ENST00000308961.5	TSL:1 MANE Select	c.311G>T	p.Arg104Leu	missense splice_region	Exon 3 of 4	ENSP00000311740.4	Q86Y39-1
ENSG00000267740	ENST00000585661.1	TSL:2	c.305G>T	p.Arg102Leu	missense splice_region	Exon 3 of 4	ENSP00000467210.1	K7EP35
NDUFA11	ENST00000592634.5	TSL:2	c.311G>T	p.Arg104Leu	missense	Exon 3 of 3	ENSP00000467706.1	K7EQ77

Frequencies

GnomAD3 genomes

AF:

0.000507

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000702

AC:

128

AN:

182298

AF XY:

0.000728

show subpopulations

Gnomad AFR exome

AF:

0.000279

Gnomad AMR exome

AF:

0.0000757

Gnomad ASJ exome

AF:

0.00517

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000124

Gnomad NFE exome

AF:

0.000849

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000921

AC:

1307

AN:

1418444

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

659

AN XY:

701126

show subpopulations

African (AFR)

AF:

0.000182

AC:

AN:

33036

American (AMR)

AF:

0.0000804

AC:

AN:

37300

Ashkenazi Jewish (ASJ)

AF:

0.00704

AC:

178

AN:

25302

East Asian (EAS)

AF:

0.00

AC:

AN:

38316

South Asian (SAS)

AF:

0.000210

AC:

AN:

80780

European-Finnish (FIN)

AF:

0.000201

AC:

AN:

49708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4692

European-Non Finnish (NFE)

AF:

0.000955

AC:

1042

AN:

1090548

Other (OTH)

AF:

0.000868

AC:

AN:

58762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

144

217

289

361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.000506

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41508

American (AMR)

AF:

0.000262

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

67970

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000930

Hom.:

Bravo

AF:

0.000582

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.00141

AC:

ExAC

AF:

0.000450

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Mitochondrial complex I deficiency, nuclear type 1 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.8

PhyloP100

5.9

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.35

Sift

Uncertain

0.011

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.92

MVP

0.50

MPC

0.25

ClinPred

0.28

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.74

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.63

dbscSNV1_RF

Benign

0.67

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