chr10-100526388-C-T

Variant names:

• chr10-100526388-C-T
• rs116226794
• NM_005004.4:c.468+11G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005004.4(NDUFB8):​c.468+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,581,526 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: NDUFB8 NM_005004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.601
• Publications: 0 publications found

Genes affected

NDUFB8 (HGNC:7703): (NADH:ubiquinone oxidoreductase subunit B8) Involved in mitochondrial respiratory chain complex I assembly. Located in endoplasmic reticulum and mitochondrion. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 32. Biomarker of Alzheimer's disease and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

NDUFB8 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 32

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with cardiomyopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000255339 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 10-100526388-C-T is Benign according to our data. Variant chr10-100526388-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168768.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005004.4. 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
	NDUFB8	NM_005004.4	MANE Select	c.468+11G>A		intron	N/A	NP_004995.1	O95169-1
	NDUFB8	NM_001284367.2		c.468+11G>A		intron	N/A	NP_001271296.1	O95169-2
	NDUFB8	NM_001284368.1		c.375+11G>A		intron	N/A	NP_001271297.1	O95169-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB8	ENST00000299166.9	TSL:1 MANE Select	c.468+11G>A		intron	N/A	ENSP00000299166.4	O95169-1
	ENSG00000255339	ENST00000557395.5	TSL:2	n.468+11G>A		intron	N/A	ENSP00000456832.1
	NDUFB8	ENST00000937696.1		c.498+11G>A		intron	N/A	ENSP00000607755.1

Frequencies

GnomAD3 genomes AF: 0.00230 AC: 350 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00783

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

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: 0.000162

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000711 AC: 157 AN: 220912 AF XY: 0.000582

Gnomad AFR exome AF: 0.00774

Gnomad AMR exome AF: 0.000759

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000153

Gnomad OTH exome AF: 0.000379

GnomAD4 exome AF: 0.000294 AC: 420 AN: 1429246 Hom.: 1 Cov.: 30 AF XY: 0.000253 AC XY: 180 AN XY: 710730

African (AFR) AF: 0.00736 AC: 230 AN: 31242

American (AMR) AF: 0.000785 AC: 27 AN: 34378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24400

East Asian (EAS) AF: 0.00 AC: 0 AN: 38876

South Asian (SAS) AF: 0.00 AC: 0 AN: 81036

European-Finnish (FIN) AF: 0.0000566 AC: 3 AN: 53048

Middle Eastern (MID) AF: 0.00112 AC: 6 AN: 5354

European-Non Finnish (NFE) AF: 0.000103 AC: 113 AN: 1102046

Other (OTH) AF: 0.000696 AC: 41 AN: 58866

GnomAD4 genome AF: 0.00230 AC: 350 AN: 152280 Hom.: 1 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74450

African (AFR) AF: 0.00780 AC: 324 AN: 41522

American (AMR) AF: 0.000784 AC: 12 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000676 Hom.: 0

Bravo AF: 0.00240

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs116226794; hg19: chr10-102286145;