rs4392868

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_148913.2(NDUFAF6):​n.957-1900A>G variant causes a intron, non coding transcript 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 NR_148913.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFAF6	NR_148913.2	n.957-1900A>G		intron_variant, non_coding_transcript_variant
NDUFAF6	NR_148914.2	n.1154-1900A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFAF6	ENST00000523184.5	n.344+4833A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.842

Alfa AF: 0.806 Hom.: 113388

Bravo AF: 0.842

Asia WGS AF: 0.956 AC: 3326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4392868; hg19: chr8-96120072;