rs7845219

Variant names:

• chr8-94925274-T-C
• rs7845219
• NM_001354516.2:c.-264+29347T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 69 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354516.2. 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	NM_001354516.2		c.-264+29347T>C		intron	N/A	NP_001341445.1	Q330K2-2
	NDUFAF6	NM_001354514.2		c.-486+29347T>C		intron	N/A	NP_001341443.1	A0A075B6P0
	NDUFAF6	NM_001354515.2		c.-269+29347T>C		intron	N/A	NP_001341444.1	A0A075B6P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF6	ENST00000396113.5	TSL:5	c.-935-20209T>C		intron	N/A	ENSP00000379419.1	A0A075B6P0
	NDUFAF6	ENST00000523378.5	TSL:3	c.-388+29347T>C		intron	N/A	ENSP00000428034.1	E5RFN5
	NDUFAF6	ENST00000519136.5	TSL:5	c.-441+29347T>C		intron	N/A	ENSP00000429585.1	E5RHX9

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

African (AFR) AF: 0.313 AC: 13008 AN: 41494

American (AMR) AF: 0.509 AC: 7780 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3468

East Asian (EAS) AF: 0.732 AC: 3770 AN: 5152

South Asian (SAS) AF: 0.588 AC: 2830 AN: 4814

European-Finnish (FIN) AF: 0.529 AC: 5583 AN: 10548

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33076 AN: 67946

Other (OTH) AF: 0.477 AC: 1005 AN: 2106

Alfa AF: 0.482 Hom.: 29534

Bravo AF: 0.453

Asia WGS AF: 0.584 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7845219; hg19: chr8-95937502;