chr16-21957483-G-A

Variant names:

• chr16-21957483-G-A
• rs1898107390
• NM_003366.4:c.184G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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]

PDZD9 (HGNC:28740): (PDZ domain containing 9)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003366.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRC2	NM_003366.4	MANE Select	c.184G>A	p.Gly62Ser	missense	Exon 3 of 14	NP_003357.2	P22695

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRC2	ENST00000268379.9	TSL:1 MANE Select	c.184G>A	p.Gly62Ser	missense	Exon 3 of 14	ENSP00000268379.4	P22695
	UQCRC2	ENST00000864414.1		c.184G>A	p.Gly62Ser	missense	Exon 3 of 15	ENSP00000534473.1
	UQCRC2	ENST00000864418.1		c.307G>A	p.Gly103Ser	missense	Exon 4 of 15	ENSP00000534477.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.45
Sift	Benign	0.27	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.91
MutPred		0.71		Gain of phosphorylation at G62 (P = 0.0571)
MVP		0.59
MPC		0.53
ClinPred		0.77	D
GERP RS		5.5
PromoterAI		-0.022	Neutral
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

Other links and lift over

dbSNP: rs1898107390; hg19: chr16-21968804;