6-96897762-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014165.4(NDUFAF4):c.40C>A(p.Leu14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,614,186 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

NDUFAF4
NM_014165.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.870

Variant links:

Genes affected

NDUFAF4 (HGNC:21034): (NADH:ubiquinone oxidoreductase complex assembly factor 4) NADH:ubiquinone oxidoreductase (complex I) 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. This gene encodes a complex I assembly factor. Mutations in this gene are a cause of mitochondrial complex I deficiency. [provided by RefSeq, Oct 2009]

NDUFAF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009006768).

BP6

Variant 6-96897762-G-T is Benign according to our data. Variant chr6-96897762-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 376856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF4	NM_014165.4 link	c.40C>A	p.Leu14Ile	missense_variant	Exon 1 of 3	ENST00000316149.8	NP_054884.1	Q9P032

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF4	ENST00000316149.8 link	c.40C>A	p.Leu14Ile	missense_variant	Exon 1 of 3	1	NM_014165.4	ENSP00000358272.4		Q9P032
NDUFAF4	ENST00000489477.1 link	n.113C>A		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

458

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.000994

AC:

250

AN:

251484

Hom.:

AF XY:

0.000795

AC XY:

108

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000272

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000480

AC:

702

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

342

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152354

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0100

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000676

Hom.:

Bravo

AF:

0.00321

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00107

AC:

130

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NDUFAF4: BP4, BS1, BS2 -

Jan 11, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mitochondrial complex 1 deficiency, nuclear type 15

Benign:1

May 17, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.7

DANN

Benign

0.74

DEOGEN2

Benign

0.18

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.37

PROVEAN

Benign

0.55

REVEL

Benign

0.23

Sift

Benign

0.39

Sift4G

Benign

0.35

Polyphen

0.46

Vest4

0.26

MVP

0.55

MPC

0.28

ClinPred

0.016

GERP RS

-6.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.048

gMVP

0.13

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