NM_016013.4:c.941C>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016013.4(NDUFAF1):c.941C>G(p.Ala314Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,611,006 control chromosomes in the GnomAD database, including 25,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1639 hom., cov: 31)

Exomes 𝑓: 0.17 ( 23827 hom. )

Consequence

NDUFAF1
NM_016013.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 9.05

Variant links:

Genes affected

NDUFAF1 (HGNC:18828): (NADH:ubiquinone oxidoreductase complex assembly factor 1) This gene encodes a complex I assembly factor protein. Complex I (NADH-ubiquinone oxidoreductase) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The encoded protein is required for assembly of complex I, and mutations in this gene are a cause of mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19. [provided by RefSeq, Dec 2011]

NDUFAF1 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=0.0019097626).

BP6

Variant 15-41387487-G-C is Benign according to our data. Variant chr15-41387487-G-C is described in ClinVar as [Benign]. Clinvar id is 129690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF1	NM_016013.4 link	c.941C>G	p.Ala314Gly	missense_variant	Exon 5 of 5	ENST00000260361.9	NP_057097.2	Q9Y375A0A024R9L0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF1	ENST00000260361.9 link	c.941C>G	p.Ala314Gly	missense_variant	Exon 5 of 5	1	NM_016013.4	ENSP00000260361.4		Q9Y375

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19476

AN:

151900

Hom.:

1637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0342

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0990

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.137

AC:

34452

AN:

251390

Hom.:

3019

AF XY:

0.142

AC XY:

19237

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.0843

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.173

AC:

252328

AN:

1458988

Hom.:

23827

Cov.:

AF XY:

0.172

AC XY:

124740

AN XY:

725980

show subpopulations

Gnomad4 AFR exome

AF:

0.0271

Gnomad4 AMR exome

AF:

0.0896

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.000706

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.128

AC:

19470

AN:

152018

Hom.:

1639

Cov.:

AF XY:

0.125

AC XY:

9288

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0341

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0999

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.175

Hom.:

1940

Bravo

AF:

0.119

TwinsUK

AF:

0.195

AC:

722

ALSPAC

AF:

0.189

AC:

729

ESP6500AA

AF:

0.0370

AC:

163

ESP6500EA

AF:

0.190

AC:

1634

ExAC

AF:

0.138

AC:

16763

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.192

EpiControl

AF:

0.182

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 20, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 03, 2015

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

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.011

Polyphen

0.95

Vest4

0.24

MPC

0.41

ClinPred

0.036

GERP RS

5.6

Varity_R

0.45

gMVP

0.59

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