Variant chr6-96889657-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014165.4(NDUFAF4):c.*1447T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 152,690 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.026 ( 77 hom., cov: 32)

Exomes 𝑓: 0.068 ( 0 hom. )

Consequence

NDUFAF4
NM_014165.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.0790

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAdExome4 highest population allele frequency = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF4	NM_014165.4 link	c.*1447T>C		3_prime_UTR_variant	3/3	ENST00000316149.8	NP_054884.1	Q9P032

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF4	ENST00000316149 link	c.*1447T>C		3_prime_UTR_variant	3/3	1	NM_014165.4	ENSP00000358272.4		Q9P032

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3882

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00873

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0806

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0340

Gnomad OTH

AF:

0.0206

GnomAD4 exome

AF:

0.0676

AC:

AN:

414

Hom.:

Cov.:

AF XY:

0.0565

AC XY:

AN XY:

248

show subpopulations

Gnomad4 FIN exome

AF:

0.0662

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.0256

AC:

3893

AN:

152276

Hom.:

Cov.:

AF XY:

0.0275

AC XY:

2044

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00900

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0806

Gnomad4 NFE

AF:

0.0340

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0322

Hom.:

Bravo

AF:

0.0200

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mitochondrial complex I deficiency, nuclear type 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

DANN

Benign

0.80

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