rs758335

Positions:

• chr16-1961125-A-G
• chr16-1961125-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004548.3(NDUFB10):​c.131-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,611,806 control chromosomes in the GnomAD database, including 544,446 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 0.86 (56770 hom., cov: 35)
  • Exomes 𝑓: 0.82 (487676 hom.)
• Consequence: NDUFB10 NM_004548.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

NDUFB10 (HGNC:7696): (NADH:ubiquinone oxidoreductase subunit B10) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 35. [provided by Alliance of Genome Resources, Apr 2022]

NDUFB10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB10	NM_004548.3	c.131-28A>G		intron_variant		ENST00000268668.11	NP_004539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB10	ENST00000268668.11	c.131-28A>G		intron_variant		1	NM_004548.3	ENSP00000268668.6

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130901 AN: 152202 Hom.: 56726 Cov.: 35

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.832

GnomAD3 exomes AF: 0.820 AC: 205346 AN: 250296 Hom.: 84903 AF XY: 0.822 AC XY: 111277 AN XY: 135382

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.698

Gnomad ASJ exome AF: 0.809

Gnomad EAS exome AF: 0.893

Gnomad SAS exome AF: 0.818

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.814

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.816 AC: 1191278 AN: 1459486 Hom.: 487676 Cov.: 44 AF XY: 0.817 AC XY: 592797 AN XY: 725874

Gnomad4 AFR exome AF: 0.969

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.804

Gnomad4 EAS exome AF: 0.843

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.887

Gnomad4 NFE exome AF: 0.811

Gnomad4 OTH exome AF: 0.825

GnomAD4 genome AF: 0.860 AC: 131005 AN: 152320 Hom.: 56770 Cov.: 35 AF XY: 0.861 AC XY: 64154 AN XY: 74472

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.831

Alfa AF: 0.815 Hom.: 34555

Bravo AF: 0.851

Asia WGS AF: 0.837 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.31
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs758335; hg19: chr16-2011126;