rs4582532

Variant names:

• chr8-94957029-G-A
• rs4582532
• NM_001354516.2:c.-263-966G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-94957029-G-A
• chr8-94957029-G-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.-263-966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,590 control chromosomes in the GnomAD database, including 18,946 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 0.50 (18946 hom., cov: 31)
• Consequence: NDUFAF6 NM_001354516.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 17 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 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF6	NM_001354516.2	c.-263-966G>A		intron_variant	Intron 1 of 10		NP_001341445.1
NDUFAF6	NM_001354514.2	c.-485-966G>A		intron_variant	Intron 1 of 11		NP_001341443.1
NDUFAF6	NM_001354515.2	c.-268-966G>A		intron_variant	Intron 1 of 9		NP_001341444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF6	ENST00000396113.5	c.-798-966G>A		intron_variant	Intron 2 of 14	5		ENSP00000379419.1
NDUFAF6	ENST00000697364.1	c.-387-966G>A		intron_variant	Intron 1 of 10			ENSP00000513278.1
NDUFAF6	ENST00000523378.5	c.-387-966G>A		intron_variant	Intron 1 of 7	3		ENSP00000428034.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75069 AN: 151474 Hom.: 18933 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.496 AC: 75126 AN: 151590 Hom.: 18946 Cov.: 31 AF XY: 0.502 AC XY: 37155 AN XY: 74072

African (AFR) AF: 0.408 AC: 16865 AN: 41300

American (AMR) AF: 0.554 AC: 8437 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3693 AN: 5148

South Asian (SAS) AF: 0.583 AC: 2802 AN: 4810

European-Finnish (FIN) AF: 0.542 AC: 5687 AN: 10490

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34224 AN: 67824

Other (OTH) AF: 0.520 AC: 1097 AN: 2110

Alfa AF: 0.489 Hom.: 2373

Bravo AF: 0.495

Asia WGS AF: 0.591 AC: 2052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.47
PhyloP100		-2.3
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: rs4582532; hg19: chr8-95969257;