rs397435

Variant names:

• chr16-1960137-G-A
• rs397435
• NM_004548.3:c.130+383G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex 1 deficiency, nuclear type 35

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NDUFB10	NM_004548.3	c.130+383G>A		intron_variant	Intron 1 of 3	ENST00000268668.11	NP_004539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB10	ENST00000268668.11	c.130+383G>A		intron_variant	Intron 1 of 3	1	NM_004548.3	ENSP00000268668.6

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

African (AFR) AF: 0.923 AC: 38250 AN: 41436

American (AMR) AF: 0.758 AC: 11576 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2777 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4564 AN: 5166

South Asian (SAS) AF: 0.818 AC: 3943 AN: 4822

European-Finnish (FIN) AF: 0.873 AC: 9215 AN: 10556

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55456 AN: 67980

Other (OTH) AF: 0.823 AC: 1738 AN: 2112

Alfa AF: 0.816 Hom.: 143011

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
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs397435; hg19: chr16-2010138;