16-21965440-C-G

Position:

• chr16-21965440-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_003366.4(UQCRC2):​c.547C>G​(p.Arg183Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UQCRC2 NM_003366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-21965440-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRC2	NM_003366.4	c.547C>G	p.Arg183Gly	missense_variant	7/14	ENST00000268379.9	NP_003357.2
PDZD9	XM_017023109.2	c.607-7823G>C		intron_variant			XP_016878598.1
PDZD9	XM_047433888.1	c.601-7823G>C		intron_variant			XP_047289844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRC2	ENST00000268379.9	c.547C>G	p.Arg183Gly	missense_variant	7/14	1	NM_003366.4	ENSP00000268379	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.;.
MutationTaster	Benign	0.97	D;D
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.3	D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.32
MutPred		0.45		Loss of solvent accessibility (P = 0.0329);Loss of solvent accessibility (P = 0.0329);.;
MVP		0.40
MPC		1.0
ClinPred		0.98	D
GERP RS		1.6
Varity_R		0.82
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs374661051; hg19: chr16-21976761;