11-68032117-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002496.4(NDUFS8):c.1-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,611,674 control chromosomes in the GnomAD database, including 432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (33 hom., cov: 33)
  • Exomes 𝑓: 0.021 (399 hom.)
• Consequence: NDUFS8 NM_002496.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-68032117-C-T is Benign according to our data. Variant chr11-68032117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1212911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0167 (2538/152330) while in subpopulation NFE AF= 0.0249 (1694/68016). AF 95% confidence interval is 0.0239. There are 33 homozygotes in gnomad4. There are 1204 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS8	NM_002496.4	c.1-35C>T		intron_variant		ENST00000313468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS8	ENST00000313468.10	c.1-35C>T		intron_variant		1	NM_002496.4	P1

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2539 AN: 152212 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.0166 AC: 4168 AN: 251084 Hom.: 52 AF XY: 0.0169 AC XY: 2294 AN XY: 135722

Gnomad AFR exome AF: 0.00400

Gnomad AMR exome AF: 0.00607

Gnomad ASJ exome AF: 0.0216

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00415

Gnomad FIN exome AF: 0.0319

Gnomad NFE exome AF: 0.0243

Gnomad OTH exome AF: 0.0171

GnomAD4 exome AF: 0.0208 AC: 30313 AN: 1459344 Hom.: 399 Cov.: 31 AF XY: 0.0204 AC XY: 14817 AN XY: 725976

Gnomad4 AFR exome AF: 0.00365

Gnomad4 AMR exome AF: 0.00655

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00425

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0234

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0167 AC: 2538 AN: 152330 Hom.: 33 Cov.: 33 AF XY: 0.0162 AC XY: 1204 AN XY: 74490

Gnomad4 AFR AF: 0.00378

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0249

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0144 Hom.: 4

Bravo AF: 0.0147

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.3
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs117961226; hg19: chr11-67799584;