16-21965442-G-T

Variant names:

• chr16-21965442-G-T
• NM_003366.4:c.549G>T
• UQCRC2 p.Arg183Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003366.4(UQCRC2):​c.549G>T​(p.Arg183Arg) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.

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.549G>T	p.Arg183Arg	synonymous	Exon 7 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.549G>T	p.Arg183Arg	synonymous	Exon 7 of 14	ENSP00000268379.4	P22695
	UQCRC2	ENST00000864414.1		c.549G>T	p.Arg183Arg	synonymous	Exon 7 of 15	ENSP00000534473.1
	UQCRC2	ENST00000864418.1		c.672G>T	p.Arg224Arg	synonymous	Exon 8 of 15	ENSP00000534477.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		1.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-21976763;