rs6822

Positions:

• chr9-122144177-C-T

Variant summary

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

The NM_014222.3(NDUFA8):​c.*64G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,611,198 control chromosomes in the GnomAD database, including 26,419 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 0.24 (5431 hom., cov: 33)
  • Exomes 𝑓: 0.16 (20988 hom.)
• Consequence: NDUFA8 NM_014222.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

Genes affected

NDUFA8 (HGNC:7692): (NADH:ubiquinone oxidoreductase subunit A8) The protein encoded by this gene belongs to the complex I 19 kDa subunit family. Mammalian complex I is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It plays an important role in transfering electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA8	NM_014222.3	c.*64G>A		3_prime_UTR_variant	4/4	ENST00000373768.4	NP_055037.1
NDUFA8	NM_001318195.2	c.381+3935G>A		intron_variant			NP_001305124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA8	ENST00000373768.4	c.*64G>A		3_prime_UTR_variant	4/4	1	NM_014222.3	ENSP00000362873.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36730 AN: 152016 Hom.: 5425 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.162 AC: 235998 AN: 1459064 Hom.: 20988 Cov.: 32 AF XY: 0.161 AC XY: 117143 AN XY: 725832

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.242 AC: 36754 AN: 152134 Hom.: 5431 Cov.: 33 AF XY: 0.241 AC XY: 17941 AN XY: 74364

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.209

Alfa AF: 0.169 Hom.: 3460

Bravo AF: 0.249

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6822; hg19: chr9-124906456; COSMIC: COSV65653803;