rs4590408

Variant names:

• chr8-95093809-A-G
• rs4590408
• ENST00000523184.5:n.214-7323A>G

Variant summary

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

The ENST00000523184.5(NDUFAF6):​n.214-7323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 152,314 control chromosomes in the GnomAD database, including 607 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 0.086 (607 hom., cov: 33)
• Consequence: NDUFAF6 ENST00000523184.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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.957-15935A>G		intron	N/A
	NDUFAF6	NR_148914.2		n.1154-15935A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF6	ENST00000523184.5	TSL:3	n.214-7323A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13088 AN: 152196 Hom.: 606 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0657

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.0860 AC: 13097 AN: 152314 Hom.: 607 Cov.: 33 AF XY: 0.0837 AC XY: 6233 AN XY: 74484

African (AFR) AF: 0.106 AC: 4409 AN: 41558

American (AMR) AF: 0.0656 AC: 1005 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3472

East Asian (EAS) AF: 0.0376 AC: 195 AN: 5188

South Asian (SAS) AF: 0.0876 AC: 423 AN: 4830

European-Finnish (FIN) AF: 0.0624 AC: 662 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0845 AC: 5750 AN: 68022

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0848 Hom.: 1762

Bravo AF: 0.0846

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.76
PhyloP100		1.3

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: rs4590408;

hg19: chr8-96106037;