Variant 11-68030915-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002496.4(NDUFS8):c.-1+182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 382,894 control chromosomes in the GnomAD database, including 22 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 0.012 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

NDUFS8
NM_002496.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.661

Variant links:

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]

NDUFS8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1516/125330) while in subpopulation AFR AF= 0.0437 (1434/32826). AF 95% confidence interval is 0.0418. There are 17 homozygotes in gnomad4. There are 724 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS8	NM_002496.4 link	c.-1+182C>T		intron_variant		ENST00000313468.10	NP_002487.1	O00217

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS8	ENST00000313468.10 link	c.-1+182C>T		intron_variant		1	NM_002496.4	ENSP00000315774.5		O00217

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1513

AN:

125226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000180

Gnomad OTH

AF:

0.00708

GnomAD3 exomes

AF:

0.00217

AC:

231

AN:

106696

Hom.:

AF XY:

0.00200

AC XY:

118

AN XY:

58962

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000127

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000919

GnomAD4 exome

AF:

0.00143

AC:

368

AN:

257564

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

165

AN XY:

146414

show subpopulations

Gnomad4 AFR exome

AF:

0.0456

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000919

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000303

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.0121

AC:

1516

AN:

125330

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

724

AN XY:

61620

show subpopulations

Gnomad4 AFR

AF:

0.0437

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000180

Gnomad4 OTH

AF:

0.00700

Alfa

AF:

0.00483

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over