11-68033027-T-G

Variant names:

• chr11-68033027-T-G
• rs3115545
• NM_002496.4:c.199+15T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002496.4(NDUFS8):​c.199+15T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,682 control chromosomes in the GnomAD database, including 799,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72710 hom., cov: 33)
  • Exomes 𝑓: 1.0 (726840 hom.)
• Consequence: NDUFS8 NM_002496.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.71
• Publications: 11 publications found

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]

MIR7113 (HGNC:49947): (microRNA 7113) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 11-68033027-T-G is Benign according to our data. Variant chr11-68033027-T-G is described in ClinVar as Benign. ClinVar VariationId is 305765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002496.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS8	NM_002496.4	MANE Select	c.199+15T>G		intron	N/A	NP_002487.1	O00217
	MIR7113	NR_106963.1		n.*105T>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS8	ENST00000313468.10	TSL:1 MANE Select	c.199+15T>G		intron	N/A	ENSP00000315774.5	O00217
	NDUFS8	ENST00000528492.1	TSL:1	c.-67+2294T>G		intron	N/A	ENSP00000432848.1	Q08E91
	NDUFS8	ENST00000852151.1		c.199+15T>G		intron	N/A	ENSP00000522210.1

Frequencies

GnomAD3 genomes AF: 0.976 AC: 148600 AN: 152188 Hom.: 72654 Cov.: 33

Gnomad AFR AF: 0.918

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

GnomAD2 exomes AF: 0.994 AC: 249062 AN: 250596 AF XY: 0.996

Gnomad AFR exome AF: 0.919

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.996

GnomAD4 exome AF: 0.997 AC: 1457356 AN: 1461376 Hom.: 726840 Cov.: 63 AF XY: 0.998 AC XY: 725291 AN XY: 727010

African (AFR) AF: 0.908 AC: 30387 AN: 33480

American (AMR) AF: 0.996 AC: 44523 AN: 44718

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26126 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39700 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86244 AN: 86254

European-Finnish (FIN) AF: 1.00 AC: 52966 AN: 52974

Middle Eastern (MID) AF: 0.991 AC: 5717 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111643 AN: 1111974

Other (OTH) AF: 0.995 AC: 60050 AN: 60382

GnomAD4 genome AF: 0.976 AC: 148714 AN: 152306 Hom.: 72710 Cov.: 33 AF XY: 0.977 AC XY: 72760 AN XY: 74470

African (AFR) AF: 0.918 AC: 38146 AN: 41550

American (AMR) AF: 0.992 AC: 15185 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5167 AN: 5168

South Asian (SAS) AF: 1.00 AC: 4832 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68003 AN: 68030

Other (OTH) AF: 0.985 AC: 2084 AN: 2116

Alfa AF: 0.980 Hom.: 9442

Bravo AF: 0.975

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Leigh syndrome (1)
-	-	1	Mitochondrial complex I deficiency, nuclear type 1 (1)
-	-	1	Mitochondrial complex I deficiency, nuclear type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.031
DANN	Benign	0.37
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3115545; hg19: chr11-67800494;