rs4392868

Variant names:

• chr8-95107844-A-G
• rs4392868
• ENST00000523184.5:n.344+4833A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-95107844-A-G
• chr8-95107844-A-T

Variant summary

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

The ENST00000523184.5(NDUFAF6):​n.344+4833A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,108 control chromosomes in the GnomAD database, including 52,886 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 0.83 (52886 hom., cov: 30)
• Consequence: NDUFAF6 ENST00000523184.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 8 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=-0.94).
• 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.957-1900A>G		intron	N/A
	NDUFAF6	NR_148914.2		n.1154-1900A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF6	ENST00000523184.5	TSL:3	n.344+4833A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126259 AN: 151990 Hom.: 52851 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.831 AC: 126350 AN: 152108 Hom.: 52886 Cov.: 30 AF XY: 0.832 AC XY: 61897 AN XY: 74354

African (AFR) AF: 0.886 AC: 36760 AN: 41492

American (AMR) AF: 0.857 AC: 13084 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2923 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5168 AN: 5174

South Asian (SAS) AF: 0.948 AC: 4579 AN: 4828

European-Finnish (FIN) AF: 0.741 AC: 7826 AN: 10560

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53254 AN: 67988

Other (OTH) AF: 0.842 AC: 1782 AN: 2116

Alfa AF: 0.812 Hom.: 182512

Bravo AF: 0.842

Asia WGS AF: 0.956 AC: 3326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.78
PhyloP100		-2.0

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: rs4392868;

hg19: chr8-96120072;