11-68036689-C-T

Position:

• chr11-68036689-C-T

Variant summary

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

The variant allele was found at a frequency of 0.74 in 1,579,622 control chromosomes in the GnomAD database, including 434,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40086 hom., cov: 34)
  • Exomes 𝑓: 0.74 (394445 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0840

Genes affected

(HGNC:):

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=-0.8).
• BP6: Variant 11-68036689-C-T is Benign according to our data. Variant chr11-68036689-C-T is described in ClinVar as [Benign]. Clinvar id is 1271580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.68036689C>T		intergenic_region
NDUFS8	NM_002496.4	c.*96C>T		downstream_gene_variant		ENST00000313468.10	NP_002487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS8	ENST00000313468.10	c.*96C>T		downstream_gene_variant		1	NM_002496.4	ENSP00000315774.5
NDUFS8	ENST00000528492.1	c.*96C>T		downstream_gene_variant		1		ENSP00000432848.1
NDUFS8	ENST00000524810.5	n.*380C>T		downstream_gene_variant		2		ENSP00000434283.1
NDUFS8	ENST00000531282.1	n.*45C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110243 AN: 152086 Hom.: 40054 Cov.: 34

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.742 AC: 1059371 AN: 1427418 Hom.: 394445 Cov.: 26 AF XY: 0.743 AC XY: 527021 AN XY: 709102

Gnomad4 AFR exome AF: 0.689

Gnomad4 AMR exome AF: 0.836

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.846

Gnomad4 SAS exome AF: 0.773

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.739

GnomAD4 genome AF: 0.725 AC: 110327 AN: 152204 Hom.: 40086 Cov.: 34 AF XY: 0.722 AC XY: 53764 AN XY: 74416

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.766

Alfa AF: 0.746 Hom.: 65725

Bravo AF: 0.740

Asia WGS AF: 0.779 AC: 2710 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	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.9
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3133269; hg19: chr11-67804156;