rs397435

Positions:

• chr16-1960137-G-A

Variant summary

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

The NM_004548.3(NDUFB10):​c.130+383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,028 control chromosomes in the GnomAD database, including 54,680 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 0.85 (54680 hom., cov: 31)
• Consequence: NDUFB10 NM_004548.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFB10	NM_004548.3	c.130+383G>A		intron_variant		ENST00000268668.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFB10	ENST00000268668.11	c.130+383G>A		intron_variant		1	NM_004548.3	P1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128489 AN: 151910 Hom.: 54644 Cov.: 31

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.846 AC: 128584 AN: 152028 Hom.: 54680 Cov.: 31 AF XY: 0.846 AC XY: 62889 AN XY: 74306

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.823

Alfa AF: 0.806 Hom.: 50414

Bravo AF: 0.836

Asia WGS AF: 0.832 AC: 2893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs397435; hg19: chr16-2010138;