chr2-201078891-T-A

Position:

• chr2-201078891-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002491.3(NDUFB3):​c.9T>A​(p.His3Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDUFB3 NM_002491.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0190

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18735024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB3	NM_002491.3	c.9T>A	p.His3Gln	missense_variant	2/3	ENST00000237889.9	NP_002482.1
NDUFB3	NM_001257102.2	c.9T>A	p.His3Gln	missense_variant	3/4		NP_001244031.1
NDUFB3	XM_011511230.4	c.9T>A	p.His3Gln	missense_variant	3/4		XP_011509532.1
NDUFB3	XM_047444488.1	c.9T>A	p.His3Gln	missense_variant	3/4		XP_047300444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB3	ENST00000237889.9	c.9T>A	p.His3Gln	missense_variant	2/3	1	NM_002491.3	ENSP00000237889	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Sep 16, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.019	.;T;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.37	T;.;.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationTaster	Benign	0.67	N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.78	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.089	.;B;B;B
Vest4		0.53
MutPred		0.13		Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);
MVP		0.88
MPC		0.16
ClinPred		0.12	T
GERP RS		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.053
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-201943614;