rs1801311

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002490.6(NDUFA6):c.26C>T(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,613,960 control chromosomes in the GnomAD database, including 93,601 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11348 hom., cov: 34)

Exomes 𝑓: 0.33 ( 82253 hom. )

Consequence

NDUFA6
NM_002490.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.918

Publications

73 publications found

Variant links:

Genes affected

NDUFA6 (HGNC:7690): (NADH:ubiquinone oxidoreductase subunit A6) This gene encodes a member of the LYR family of proteins that contain a highly conserved tripeptide (LYR) motif near the N-terminus. The encoded protein is an accessory subunit of NADH: ubiquinone oxidorerductase (Complex I), which is the largest enzyme of the mitochondrial membrane respiratory chain. Complex I functions in electron transfer from NADH to the respiratory chain. [provided by RefSeq, Oct 2016]

NDUFA6 links:

NDUFA6-DT (HGNC:45273): (NDUFA6 divergent transcript)

NDUFA6-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8364191E-4).

BP6

Variant 22-42090719-G-A is Benign according to our data. Variant chr22-42090719-G-A is described in ClinVar as Benign. ClinVar VariationId is 1244198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA6	NM_002490.6 link	c.26C>T	p.Ala9Val	missense_variant	Exon 1 of 3	ENST00000498737.8	NP_002481.3	P56556A0A2Y9D025
NDUFA6-DT	NR_034118.2 link	n.-214G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA6	ENST00000498737.8 link	c.26C>T	p.Ala9Val	missense_variant	Exon 1 of 3	1	NM_002490.6	ENSP00000418842.3		P56556

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57170

AN:

152038

Hom.:

11312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.383

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.377

GnomAD2 exomes

AF:

0.333

AC:

83712

AN:

251308

AF XY:

0.337

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.331

AC:

483755

AN:

1461804

Hom.:

82253

Cov.:

AF XY:

0.333

AC XY:

242391

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.511

AC:

17106

AN:

33480

American (AMR)

AF:

0.282

AC:

12592

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

10541

AN:

26134

East Asian (EAS)

AF:

0.153

AC:

6078

AN:

39700

South Asian (SAS)

AF:

0.380

AC:

32785

AN:

86258

European-Finnish (FIN)

AF:

0.378

AC:

20151

AN:

53348

Middle Eastern (MID)

AF:

0.422

AC:

2433

AN:

5768

European-Non Finnish (NFE)

AF:

0.325

AC:

361057

AN:

1111996

Other (OTH)

AF:

0.348

AC:

21012

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

23416

46831

70247

93662

117078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11730

23460

35190

46920

58650

<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:

0.376

AC:

57256

AN:

152156

Hom.:

11348

Cov.:

AF XY:

0.378

AC XY:

28094

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.497

AC:

20620

AN:

41498

American (AMR)

AF:

0.332

AC:

5081

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1356

AN:

3468

East Asian (EAS)

AF:

0.150

AC:

774

AN:

5166

South Asian (SAS)

AF:

0.382

AC:

1845

AN:

4832

European-Finnish (FIN)

AF:

0.383

AC:

4049

AN:

10580

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.329

AC:

22395

AN:

67994

Other (OTH)

AF:

0.375

AC:

792

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1876

3753

5629

7506

9382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.346

Hom.:

30111

Bravo

AF:

0.374

TwinsUK

AF:

0.316

AC:

1171

ALSPAC

AF:

0.316

AC:

1219

ESP6500AA

AF:

0.493

AC:

2174

ESP6500EA

AF:

0.336

AC:

2889

ExAC

AF:

0.337

AC:

40891

Asia WGS

AF:

0.281

AC:

977

AN:

3478

EpiCase

AF:

0.339

EpiControl

AF:

0.345

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mitochondrial complex I deficiency, nuclear type 33

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

NDUFA6-related disorder

Benign:1

Nov 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.46

MetaRNN

Benign

0.00018

T;T

MetaSVM

Benign

-0.93

PhyloP100

0.92

PrimateAI

Benign

0.35

REVEL

Benign

0.094

Sift4G

Benign

0.10

.;T

Vest4

0.13

MPC

0.21

ClinPred

0.053

GERP RS

2.4

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.42

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over