NM_005004.4:c.469-222_469-220delTCT

Variant names:

• chr10-100524148-GAGA-G
• rs772321168
• NM_005004.4:c.469-222_469-220delTCT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_005004.4(NDUFB8):​c.469-222_469-220delTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000357 in 1,569,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: NDUFB8 NM_005004.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.509
• 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 -1 ACMG points.

• BP6: Variant 10-100524148-GAGA-G is Benign according to our data. Variant chr10-100524148-GAGA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3048758.Status of the report is no_assertion_criteria_provided, 0 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.469-222_469-220delTCT		intron	N/A	NP_004995.1	O95169-1
	NDUFB8	NM_001284367.2		c.469-12_469-10delTCT		intron	N/A	NP_001271296.1	O95169-2
	NDUFB8	NM_001284368.1		c.376-222_376-220delTCT		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.469-222_469-220delTCT		intron	N/A	ENSP00000299166.4	O95169-1
	ENSG00000255339	ENST00000557395.5	TSL:2	n.469-12_469-10delTCT		intron	N/A	ENSP00000456832.1
	NDUFB8	ENST00000937696.1		c.499-222_499-220delTCT		intron	N/A	ENSP00000607755.1

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 31 AN: 151514 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00171

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: 0.00

Gnomad OTH AF: 0.000962

GnomAD2 exomes AF: 0.0000269 AC: 5 AN: 186196 AF XY: 0.0000200

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000397

GnomAD4 exome AF: 0.0000176 AC: 25 AN: 1417890 Hom.: 0 AF XY: 0.0000142 AC XY: 10 AN XY: 701804

African (AFR) AF: 0.00 AC: 0 AN: 32538

American (AMR) AF: 0.000470 AC: 18 AN: 38318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 37752

South Asian (SAS) AF: 0.00 AC: 0 AN: 81108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1088192

Other (OTH) AF: 0.0000848 AC: 5 AN: 58928

GnomAD4 genome AF: 0.000204 AC: 31 AN: 151626 Hom.: 0 Cov.: 31 AF XY: 0.000270 AC XY: 20 AN XY: 74066

African (AFR) AF: 0.0000726 AC: 3 AN: 41296

American (AMR) AF: 0.00171 AC: 26 AN: 15202

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67902

Other (OTH) AF: 0.000951 AC: 2 AN: 2102

Alfa AF: 0.0000434 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NDUFB8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs772321168; hg19: chr10-102283905;