22-29769682-T-C

Variant names:

• chr22-29769682-T-C
• NM_013387.4:c.155T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013387.4(UQCR10):​c.155T>C​(p.Leu52Pro) variant causes a missense change. 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: 33)
• Consequence: UQCR10 NM_013387.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46

Genes affected

UQCR10 (HGNC:30863): (ubiquinol-cytochrome c reductase, complex III subunit X) UCRC is a subunit of mitochondrial complex III (ubiquinol-cytochrome c reductase; EC 1.10.2.2), which forms the middle segment of the respiratory chain of the inner mitochondrial membrane (Schagger et al., 1995 [PubMed 8592474]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCR10	NM_013387.4	c.155T>C	p.Leu52Pro	missense_variant	Exon 2 of 2	ENST00000330029.6	NP_037519.2
UQCR10	NM_001003684.2	c.*25T>C		3_prime_UTR_variant	Exon 2 of 2		NP_001003684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCR10	ENST00000330029.6	c.155T>C	p.Leu52Pro	missense_variant	Exon 2 of 2	1	NM_013387.4	ENSP00000332887.6
UQCR10	ENST00000401406.3	c.*25T>C		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000384962.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.155T>C (p.L52P) alteration is located in exon 2 (coding exon 2) of the UQCR10 gene. This alteration results from a T to C substitution at nucleotide position 155, causing the leucine (L) at amino acid position 52 to be replaced by a proline (P). 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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.56	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.82
MutPred		0.75		Gain of disorder (P = 0.0043);
MVP		0.57
MPC		1.2
ClinPred		0.98	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.94
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-30165671;