8-95114904-G-A

Variant names:

• chr8-95114904-G-A
• rs16917360
• ENST00000523184.5:n.345-632G>A

Variant summary

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

The ENST00000523184.5(NDUFAF6):​n.345-632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 152,126 control chromosomes in the GnomAD database, including 170 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 0.045 (170 hom., cov: 31)
• Consequence: NDUFAF6 ENST00000523184.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 3 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 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0657 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF6	NR_148913.2		n.1067-632G>A		intron	N/A
	NDUFAF6	NR_148914.2		n.1264-632G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF6	ENST00000523184.5	TSL:3	n.345-632G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6867 AN: 152008 Hom.: 170 Cov.: 31

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0451 AC: 6864 AN: 152126 Hom.: 170 Cov.: 31 AF XY: 0.0448 AC XY: 3331 AN XY: 74380

African (AFR) AF: 0.0152 AC: 630 AN: 41506

American (AMR) AF: 0.0581 AC: 887 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3466

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5182

South Asian (SAS) AF: 0.0719 AC: 346 AN: 4810

European-Finnish (FIN) AF: 0.0534 AC: 565 AN: 10576

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0588 AC: 3996 AN: 67998

Other (OTH) AF: 0.0454 AC: 96 AN: 2114

Alfa AF: 0.0534 Hom.: 458

Bravo AF: 0.0427

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.70
PhyloP100		0.77

Splicing

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

Other links and lift over

dbSNP: rs16917360; hg19: chr8-96127132;