rs4735337

Positions:

• chr8-94961237-T-C
• chr8-94961237-T-G

Variant summary

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

The NM_001354516.2(NDUFAF6):​c.-79+3058T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,030 control chromosomes in the GnomAD database, including 19,913 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 0.51 (19913 hom., cov: 33)
• Consequence: NDUFAF6 NM_001354516.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF6	NM_001354514.2	c.-301+3058T>C		intron_variant			NP_001341443.1
NDUFAF6	NM_001354515.2	c.-84+3058T>C		intron_variant			NP_001341444.1
NDUFAF6	NM_001354516.2	c.-79+3058T>C		intron_variant			NP_001341445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF6	ENST00000396111.6	c.-199+3058T>C		intron_variant		5		ENSP00000379417
NDUFAF6	ENST00000396113.5	c.-614+3058T>C		intron_variant		5		ENSP00000379419
NDUFAF6	ENST00000519136.5	c.-256+3058T>C		intron_variant		5		ENSP00000429585

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76931 AN: 151912 Hom.: 19902 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.506 AC: 76984 AN: 152030 Hom.: 19913 Cov.: 33 AF XY: 0.513 AC XY: 38088 AN XY: 74302

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.531

Alfa AF: 0.526 Hom.: 42496

Bravo AF: 0.504

Asia WGS AF: 0.594 AC: 2065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4735337; hg19: chr8-95973465;