16-21957505-G-A

Position:

• chr16-21957505-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003366.4(UQCRC2):​c.206G>A​(p.Ser69Asn) 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

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRC2	NM_003366.4	c.206G>A	p.Ser69Asn	missense_variant	3/14	ENST00000268379.9	NP_003357.2
PDZD9	XM_017023109.2			downstream_gene_variant			XP_016878598.1
PDZD9	XM_047433888.1			downstream_gene_variant			XP_047289844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRC2	ENST00000268379.9	c.206G>A	p.Ser69Asn	missense_variant	3/14	1	NM_003366.4	ENSP00000268379	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial complex III deficiency nuclear type 5 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Apr 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.;.;T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	3.7	H;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D;.;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D;.;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.90
MutPred		0.89		Loss of phosphorylation at S69 (P = 0.0485);Loss of phosphorylation at S69 (P = 0.0485);Loss of phosphorylation at S69 (P = 0.0485);.;
MVP		0.64
MPC		0.91
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.71

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: chr16-21968826;