NM_005002.5:c.13G>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005002.5(NDUFA9):c.13G>C(p.Ala5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,604,258 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 30 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 35 hom. )

Consequence

NDUFA9
NM_005002.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.147

Variant links:

Genes affected

NDUFA9 (HGNC:7693): (NADH:ubiquinone oxidoreductase subunit A9) The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane. A pseudogene has been identified on chromosome 12. [provided by RefSeq, May 2010]

NDUFA9 links:

ENSG00000255639 (HGNC:):

ENSG00000255639 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=0.0033494532).

BP6

Variant 12-4649139-G-C is Benign according to our data. Variant chr12-4649139-G-C is described in ClinVar as [Benign]. Clinvar id is 138450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-4649139-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1583/152348) while in subpopulation AFR AF= 0.036 (1498/41578). AF 95% confidence interval is 0.0345. There are 30 homozygotes in gnomad4. There are 764 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA9	NM_005002.5 link	c.13G>C	p.Ala5Pro	missense_variant	Exon 1 of 11	ENST00000266544.10	NP_004993.1	Q16795

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NDUFA9	ENST00000266544.10 link	c.13G>C	p.Ala5Pro	missense_variant	Exon 1 of 11	1	NM_005002.5	ENSP00000266544.5	Q16795
ENSG00000255639	ENST00000648836.1 link	c.13G>C	p.Ala5Pro	missense_variant	Exon 1 of 15			ENSP00000497305.1	A0A3B3ISG8
ENSG00000272921	ENST00000536588.1 link	n.*50-5153G>C		intron_variant	Intron 2 of 6	3		ENSP00000445121.1	H0YGX0

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1578

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

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:

0.0000441

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00227

AC:

524

AN:

230680

Hom.:

AF XY:

0.00170

AC XY:

212

AN XY:

124478

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000357

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000385

Gnomad OTH exome

AF:

0.000530

GnomAD4 exome

AF:

0.00107

AC:

1555

AN:

1451910

Hom.:

Cov.:

AF XY:

0.000917

AC XY:

661

AN XY:

721032

show subpopulations

Gnomad4 AFR exome

AF:

0.0400

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000595

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.0104

AC:

1583

AN:

152348

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

764

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0360

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.0121

ESP6500AA

AF:

0.0381

AC:

168

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00275

AC:

333

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 04, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Feb 09, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.20

Sift

Benign

0.079

T;.

Sift4G

Benign

0.074

T;.

Polyphen

0.89

P;.

Vest4

0.34

MVP

0.67

MPC

0.33

ClinPred

0.0099

GERP RS

0.53

Varity_R

0.39

gMVP

0.68

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