rs7000734

Variant names:

• chr8-95114802-G-A
• rs7000734
• ENST00000523184.5:n.345-734G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523184.5(NDUFAF6):​n.345-734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,254 control chromosomes in the GnomAD database, including 54,288 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54288 hom., cov: 33)
• Consequence: NDUFAF6 ENST00000523184.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 9 publications found

Genes affected

NDUFAF6 (HGNC:28625): (NADH:ubiquinone oxidoreductase complex assembly factor 6) This gene encodes a protein that localizes to mitochondria and contains a predicted phytoene synthase domain. The encoded protein plays an important role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain through regulation of subunit ND1 biogenesis. Mutations in this gene are associated with complex I enzymatic deficiency. [provided by RefSeq, Nov 2011]

NDUFAF6 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex I deficiency, nuclear type 17

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• primary Fanconi syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi renotubular syndrome 5

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523184.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF6	NR_148913.2		n.1067-734G>A		intron	N/A
	NDUFAF6	NR_148914.2		n.1264-734G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF6	ENST00000523184.5	TSL:3	n.345-734G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127871 AN: 152136 Hom.: 54244 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.850

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.841 AC: 127974 AN: 152254 Hom.: 54288 Cov.: 33 AF XY: 0.842 AC XY: 62660 AN XY: 74448

African (AFR) AF: 0.921 AC: 38240 AN: 41530

American (AMR) AF: 0.858 AC: 13129 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2924 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5181 AN: 5186

South Asian (SAS) AF: 0.949 AC: 4580 AN: 4828

European-Finnish (FIN) AF: 0.742 AC: 7865 AN: 10596

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53285 AN: 68026

Other (OTH) AF: 0.848 AC: 1793 AN: 2114

Alfa AF: 0.818 Hom.: 96384

Bravo AF: 0.853

Asia WGS AF: 0.960 AC: 3340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.24
PhyloP100		-0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7000734;

hg19: chr8-96127030;