NM_002491.3:c.-2-1167C>T

Variant names:

• chr2-201077714-C-T
• rs10194168
• NM_002491.3:c.-2-1167C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002491.3(NDUFB3):​c.-2-1167C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,166 control chromosomes in the GnomAD database, including 4,448 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 0.22 (4448 hom., cov: 32)
• Consequence: NDUFB3 NM_002491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 7 publications found

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]

NDUFB3 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 25

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB3	NM_002491.3	MANE Select	c.-2-1167C>T		intron	N/A	NP_002482.1
	NDUFB3	NM_001257102.2		c.-2-1167C>T		intron	N/A	NP_001244031.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB3	ENST00000237889.9	TSL:1 MANE Select	c.-2-1167C>T		intron	N/A	ENSP00000237889.4
	NDUFB3	ENST00000433898.5	TSL:2	c.-2-1167C>T		intron	N/A	ENSP00000410600.1
	NDUFB3	ENST00000450023.6	TSL:3	c.-2-1167C>T		intron	N/A	ENSP00000401834.2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32981 AN: 152048 Hom.: 4440 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.217 AC: 33026 AN: 152166 Hom.: 4448 Cov.: 32 AF XY: 0.213 AC XY: 15819 AN XY: 74398

African (AFR) AF: 0.374 AC: 15515 AN: 41462

American (AMR) AF: 0.163 AC: 2495 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.00848 AC: 44 AN: 5190

South Asian (SAS) AF: 0.0711 AC: 343 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1747 AN: 10586

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11546 AN: 68022

Other (OTH) AF: 0.204 AC: 432 AN: 2116

Alfa AF: 0.203 Hom.: 474

Bravo AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.57
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10194168; hg19: chr2-201942437;