3-179615019-G-C

Position:

• chr3-179615019-G-C

Variant summary

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

The NM_002492.4(NDUFB5):​c.173G>C​(p.Arg58Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDUFB5 NM_002492.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

Genes affected

NDUFB5 (HGNC:7700): (NADH:ubiquinone oxidoreductase subunit B5) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ENSG00000288698 (HGNC:):

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=0.14594185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB5	NM_002492.4	c.173G>C	p.Arg58Thr	missense_variant	2/6	ENST00000259037.8	NP_002483.1
NDUFB5	NM_001199958.2	c.173G>C	p.Arg58Thr	missense_variant	2/5		NP_001186887.1
NDUFB5	NM_001199957.2	c.125-1964G>C		intron_variant			NP_001186886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB5	ENST00000259037.8	c.173G>C	p.Arg58Thr	missense_variant	2/6	1	NM_002492.4	ENSP00000259037.3
ENSG00000288698	ENST00000680408.1	n.173G>C		non_coding_transcript_exon_variant	2/26			ENSP00000506198.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.173G>C (p.R58T) alteration is located in exon 2 (coding exon 2) of the NDUFB5 gene. This alteration results from a G to C substitution at nucleotide position 173, causing the arginine (R) at amino acid position 58 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.7
DANN	Benign	0.94
DEOGEN2	Benign	0.068	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.45	N;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.049
Sift	Benign	0.26	T;.
Sift4G	Uncertain	0.034	D;D
Polyphen		0.0080	B;.
Vest4		0.27
MutPred		0.62		Loss of MoRF binding (P = 0.0345);Loss of MoRF binding (P = 0.0345);
MVP		0.19
MPC		0.27
ClinPred		0.15	T
GERP RS		0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.14
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-179332807;