5-132867023-C-T

Position:

• chr5-132867023-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014402.5(UQCRQ):​c.142C>T​(p.Arg48Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UQCRQ NM_014402.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80

Genes affected

UQCRQ (HGNC:29594): (ubiquinol-cytochrome c reductase complex III subunit VII) This gene encodes a ubiquinone-binding protein of low molecular mass. This protein is a small core-associated protein and a subunit of ubiquinol-cytochrome c reductase complex III, which is part of the mitochondrial respiratory chain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRQ	NM_014402.5	c.142C>T	p.Arg48Cys	missense_variant	2/3	ENST00000378670.8	NP_055217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRQ	ENST00000378670.8	c.142C>T	p.Arg48Cys	missense_variant	2/3	1	NM_014402.5	ENSP00000367939	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 02, 2024

The c.142C>T (p.R48C) alteration is located in exon 2 (coding exon 1) of the UQCRQ gene. This alteration results from a C to T substitution at nucleotide position 142, causing the arginine (R) at amino acid position 48 to be replaced by a cysteine (C). 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	0.19
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Uncertain	0.73	D;D;D
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.73	.;.;T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.015	B;B;B
Vest4		0.58
MutPred		0.54		Loss of MoRF binding (P = 8e-04);Loss of MoRF binding (P = 8e-04);Loss of MoRF binding (P = 8e-04);
MVP		0.73
MPC		0.84
ClinPred		0.97	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.22		Position offset: 12

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

Publications

LitVar

Other links and lift over

dbSNP: rs765042690; hg19: chr5-132202715;