rs7000734

Positions:

• chr8-95114802-G-A

Variant summary

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

The NR_148913.2(NDUFAF6):​n.1067-734G>A 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 0.841 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 NR_148913.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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=-0.88).
• 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.1067-734G>A		intron_variant, non_coding_transcript_variant
NDUFAF6	NR_148914.2	n.1264-734G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFAF6	ENST00000523184.5	n.345-734G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.949

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.848

Alfa AF: 0.809 Hom.: 60319

Bravo AF: 0.853

Asia WGS AF: 0.960 AC: 3340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7000734; hg19: chr8-96127030;