rs7845219

chr8-94925274-T-C

Variant summary

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

The NM_001354516.2(NDUFAF6):c.-264+29347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,022 control chromosomes in the GnomAD database, including 16,671 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 0.46 (16671 hom., cov: 32)
• Consequence: NDUFAF6 NM_001354516.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.835

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFAF6	NM_001354514.2	c.-486+29347T>C		intron_variant
NDUFAF6	NM_001354515.2	c.-269+29347T>C		intron_variant
NDUFAF6	NM_001354516.2	c.-264+29347T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFAF6	ENST00000396113.5	c.-935-20209T>C		intron_variant		5
NDUFAF6	ENST00000519136.5	c.-441+29347T>C		intron_variant		5
NDUFAF6	ENST00000523378.5	c.-388+29347T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69264 AN: 151904 Hom.: 16661 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.456 AC: 69315 AN: 152022 Hom.: 16671 Cov.: 32 AF XY: 0.463 AC XY: 34376 AN XY: 74300

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.477

Alfa AF: 0.489 Hom.: 18460

Bravo AF: 0.453

Asia WGS AF: 0.584 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	16
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: rs7845219; hg19: chr8-95937502;