10-100523888-T-C

Variant names:

• chr10-100523888-T-C
• NM_005004.4:c.510A>G
• NDUFB8 p.Arg170Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005004.4(NDUFB8):​c.510A>G​(p.Arg170Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NDUFB8 NM_005004.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.785 with no splicing effect.

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.510A>G	p.Arg170Arg	synonymous	Exon 5 of 5	NP_004995.1	O95169-1
	NDUFB8	NM_001284368.1		c.417A>G	p.Arg139Arg	synonymous	Exon 5 of 5	NP_001271297.1	O95169-3
	NDUFB8	NM_001284367.2		c.*201A>G		3_prime_UTR	Exon 5 of 5	NP_001271296.1	O95169-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB8	ENST00000299166.9	TSL:1 MANE Select	c.510A>G	p.Arg170Arg	synonymous	Exon 5 of 5	ENSP00000299166.4	O95169-1
	ENSG00000255339	ENST00000557395.5	TSL:2	n.*112+89A>G		intron	N/A	ENSP00000456832.1
	NDUFB8	ENST00000937696.1		c.540A>G	p.Arg180Arg	synonymous	Exon 5 of 5	ENSP00000607755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.6
DANN	Benign	0.72
PhyloP100		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-102283645;