chr5-132866943-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014402.5(UQCRQ):​c.62C>T​(p.Pro21Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

UQCRQ
NM_014402.5 missense

Scores

9
8
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.39
Variant links:
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]
GDF9 (HGNC:4224): (growth differentiation factor 9) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates ovarian function. Reduced expression of this gene may be associated with polycystic ovary syndrome and mutations in this gene may be more common in mothers of dizygotic twins. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

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, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UQCRQNM_014402.5 linkc.62C>T p.Pro21Leu missense_variant Exon 2 of 3 ENST00000378670.8 NP_055217.2 O14949

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UQCRQENST00000378670.8 linkc.62C>T p.Pro21Leu missense_variant Exon 2 of 3 1 NM_014402.5 ENSP00000367939.3 O14949

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461720
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.000122
Hom.:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.62C>T (p.P21L) 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 62, causing the proline (P) at amino acid position 21 to be replaced by a leucine (L). 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
0.64
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
D;D;D
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
.;.;D
M_CAP
Pathogenic
0.56
D
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Uncertain
0.74
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-8.2
D;D;D
REVEL
Pathogenic
0.82
Sift
Uncertain
0.025
D;D;D
Sift4G
Uncertain
0.047
D;D;D
Polyphen
0.86
P;P;P
Vest4
0.99
MutPred
0.86
Loss of disorder (P = 0.0648);Loss of disorder (P = 0.0648);Loss of disorder (P = 0.0648);
MVP
0.94
MPC
1.1
ClinPred
1.0
D
GERP RS
4.7
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.92
gMVP
0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1759642049; hg19: chr5-132202635; API