rs10194347

Positions:

• chr2-201077757-G-A
• chr2-201077757-G-T

Variant summary

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

The NM_002491.3(NDUFB3):​c.-2-1124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 151,966 control chromosomes in the GnomAD database, including 2,401 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 0.17 (2401 hom., cov: 32)
• Consequence: NDUFB3 NM_002491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

Genes affected

NDUFB3 (HGNC:7698): (NADH:ubiquinone oxidoreductase subunit B3) This gene encodes an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which is the first enzyme in the electron transport chain of mitochondria. This protein localizes to the inner membrane of the mitochondrion as a single-pass membrane protein. Mutations in this gene contribute to mitochondrial complex 1 deficiency. Alternative splicing results in multiple transcript variants encoding the same protein. Humans have multiple pseudogenes of this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFB3	NM_002491.3	c.-2-1124G>A		intron_variant		ENST00000237889.9
NDUFB3	NM_001257102.2	c.-2-1124G>A		intron_variant
NDUFB3	XM_011511230.4	c.-2-1124G>A		intron_variant
NDUFB3	XM_047444488.1	c.-2-1124G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFB3	ENST00000237889.9	c.-2-1124G>A		intron_variant		1	NM_002491.3	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25803 AN: 151848 Hom.: 2395 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.170 AC: 25831 AN: 151966 Hom.: 2401 Cov.: 32 AF XY: 0.167 AC XY: 12404 AN XY: 74294

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.172

Alfa AF: 0.173 Hom.: 2942

Bravo AF: 0.172

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10194347; hg19: chr2-201942480;