chr9-122152334-C-T

Position:

• chr9-122152334-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014222.3(NDUFA8):​c.126G>A​(p.Glu42Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.562 in 1,613,720 control chromosomes in the GnomAD database, including 266,611 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 0.44 (17912 hom., cov: 31)
  • Exomes 𝑓: 0.57 (248699 hom.)
• Consequence: NDUFA8 NM_014222.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA8	NM_014222.3	c.126G>A	p.Glu42Glu	synonymous_variant	2/4	ENST00000373768.4	NP_055037.1
NDUFA8	NM_001318195.2	c.126G>A	p.Glu42Glu	synonymous_variant	2/4		NP_001305124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA8	ENST00000373768.4	c.126G>A	p.Glu42Glu	synonymous_variant	2/4	1	NM_014222.3	ENSP00000362873.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67018 AN: 151816 Hom.: 17921 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.479

GnomAD3 exomes AF: 0.506 AC: 127077 AN: 251254 Hom.: 34733 AF XY: 0.519 AC XY: 70525 AN XY: 135814

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.232

Gnomad SAS exome AF: 0.523

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.605

Gnomad OTH exome AF: 0.533

GnomAD4 exome AF: 0.575 AC: 839816 AN: 1461786 Hom.: 248699 Cov.: 53 AF XY: 0.575 AC XY: 418044 AN XY: 727184

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.613

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.441 AC: 67008 AN: 151934 Hom.: 17912 Cov.: 31 AF XY: 0.438 AC XY: 32528 AN XY: 74198

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.478

Alfa AF: 0.549 Hom.: 24435

Bravo AF: 0.419

Asia WGS AF: 0.342 AC: 1191 AN: 3478

EpiCase AF: 0.613

EpiControl AF: 0.615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Benign	0.63

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: rs4679; hg19: chr9-124914613; COSMIC: COSV65653264;