16-21957483-G-A

Position:

• chr16-21957483-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003366.4(UQCRC2):​c.184G>A​(p.Gly62Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UQCRC2 NM_003366.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.50

Genes affected

UQCRC2 (HGNC:12586): (ubiquinol-cytochrome c reductase core protein 2) The protein encoded by this gene is located in the mitochondrion, where it is part of the ubiquinol-cytochrome c reductase complex (also known as complex III). This complex constitutes a part of the mitochondrial respiratory chain. Defects in this gene are a cause of mitochondrial complex III deficiency nuclear type 5. [provided by RefSeq, Jul 2015]

UQCRC2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRC2	NM_003366.4	c.184G>A	p.Gly62Ser	missense_variant	3/14	ENST00000268379.9	NP_003357.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRC2	ENST00000268379.9	c.184G>A	p.Gly62Ser	missense_variant	3/14	1	NM_003366.4	ENSP00000268379.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 08, 2024

The c.184G>A (p.G62S) alteration is located in exon 3 (coding exon 3) of the UQCRC2 gene. This alteration results from a G to A substitution at nucleotide position 184, causing the glycine (G) at amino acid position 62 to be replaced by a serine (S). 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	0.29
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;.;.;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.99	N;.;N;N
REVEL	Uncertain	0.45
Sift	Benign	0.27	T;.;T;T
Sift4G	Benign	0.17	T;D;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.91
MutPred		0.71		Gain of phosphorylation at G62 (P = 0.0571);Gain of phosphorylation at G62 (P = 0.0571);Gain of phosphorylation at G62 (P = 0.0571);.;
MVP		0.59
MPC		0.53
ClinPred		0.77	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.79

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: rs1898107390; hg19: chr16-21968804;