11-68032013-G-C

Position:

• chr11-68032013-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002496.4(NDUFS8):​c.1-139G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,250,306 control chromosomes in the GnomAD database, including 848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (479 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (369 hom.)
• Consequence: NDUFS8 NM_002496.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.508

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=-0.9).
• BP6: Variant 11-68032013-G-C is Benign according to our data. Variant chr11-68032013-G-C is described in ClinVar as [Benign]. Clinvar id is 1269472.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS8	NM_002496.4	c.1-139G>C		intron_variant		ENST00000313468.10	NP_002487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS8	ENST00000313468.10	c.1-139G>C		intron_variant		1	NM_002496.4	ENSP00000315774	P1

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6897 AN: 152208 Hom.: 473 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.00785 AC: 8617 AN: 1097980 Hom.: 369 AF XY: 0.00740 AC XY: 4150 AN XY: 560636

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.00633

Gnomad4 FIN exome AF: 0.0000212

Gnomad4 NFE exome AF: 0.00268

Gnomad4 OTH exome AF: 0.0146

GnomAD4 genome AF: 0.0455 AC: 6926 AN: 152326 Hom.: 479 Cov.: 33 AF XY: 0.0446 AC XY: 3325 AN XY: 74484

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00359

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0327 Hom.: 31

Bravo AF: 0.0518

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs11824781; hg19: chr11-67799480;