rs3818638

Positions:

• chr9-122144444-T-C

Variant summary

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

The NM_014222.3(NDUFA8):​c.382-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 1,498,066 control chromosomes in the GnomAD database, including 422,053 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 0.76 (44464 hom., cov: 33)
  • Exomes 𝑓: 0.75 (377589 hom.)
• Consequence: NDUFA8 NM_014222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA8	NM_014222.3	c.382-66A>G		intron_variant		ENST00000373768.4	NP_055037.1
NDUFA8	NM_001318195.2	c.381+3668A>G		intron_variant			NP_001305124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA8	ENST00000373768.4	c.382-66A>G		intron_variant		1	NM_014222.3	ENSP00000362873.3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115571 AN: 152072 Hom.: 44440 Cov.: 33

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.746 AC: 1004298 AN: 1345876 Hom.: 377589 AF XY: 0.745 AC XY: 503286 AN XY: 675654

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.684

Gnomad4 ASJ exome AF: 0.767

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.768

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.731

GnomAD4 genome AF: 0.760 AC: 115643 AN: 152190 Hom.: 44464 Cov.: 33 AF XY: 0.755 AC XY: 56163 AN XY: 74396

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.737

Alfa AF: 0.756 Hom.: 88756

Bravo AF: 0.756

Asia WGS AF: 0.581 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.41

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: rs3818638; hg19: chr9-124906723; COSMIC: COSV65653372;