11-68032459-T-C

Position:

• chr11-68032459-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002496.4(NDUFS8):​c.109+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,561,342 control chromosomes in the GnomAD database, including 40,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3881 hom., cov: 33)
  • Exomes 𝑓: 0.23 (36746 hom.)
• Consequence: NDUFS8 NM_002496.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0630

Genes affected

NDUFS8 (HGNC:7715): (NADH:ubiquinone oxidoreductase core subunit S8) This gene encodes a subunit of mitochondrial NADH:ubiquinone oxidoreductase, or Complex I, a multimeric enzyme of the respiratory chain responsible for NADH oxidation, ubiquinone reduction, and the ejection of protons from mitochondria. The encoded protein is involved in the binding of two of the six to eight iron-sulfur clusters of Complex I and, as such, is required in the electron transfer process. Mutations in this gene have been associated with Leigh syndrome. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 11-68032459-T-C is Benign according to our data. Variant chr11-68032459-T-C is described in ClinVar as [Benign]. Clinvar id is 1288362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS8	NM_002496.4	c.109+123T>C		intron_variant		ENST00000313468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS8	ENST00000313468.10	c.109+123T>C		intron_variant		1	NM_002496.4	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33698 AN: 152012 Hom.: 3880 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.225 AC: 317390 AN: 1409212 Hom.: 36746 Cov.: 38 AF XY: 0.224 AC XY: 155813 AN XY: 696896

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.222 AC: 33713 AN: 152130 Hom.: 3881 Cov.: 33 AF XY: 0.213 AC XY: 15855 AN XY: 74386

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0962

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.227

Alfa AF: 0.230 Hom.: 5545

Bravo AF: 0.229

Asia WGS AF: 0.189 AC: 661 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.5
DANN	Benign	0.76

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: rs2075626; hg19: chr11-67799926; COSMIC: COSV50292376; COSMIC: COSV50292376;