Genetic Variant UQCR10:p.Lys9Glu (chr22-29767423-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013387.4(UQCR10):c.25A>G(p.Lys9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000874 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

UQCR10
NM_013387.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.670

Variant links:

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]

UQCR10 links:

ENSG00000287967 (HGNC:):

ENSG00000287967 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021468371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCR10	NM_013387.4 link	c.25A>G	p.Lys9Glu	missense_variant	Exon 1 of 2	ENST00000330029.6	NP_037519.2	Q9UDW1-1
UQCR10	NM_001003684.2 link	c.25A>G	p.Lys9Glu	missense_variant	Exon 1 of 2		NP_001003684.1	Q9UDW1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UQCR10	ENST00000330029.6 link	c.25A>G	p.Lys9Glu	missense_variant	Exon 1 of 2	1	NM_013387.4	ENSP00000332887.6	Q9UDW1-1
UQCR10	ENST00000401406.3 link	c.25A>G	p.Lys9Glu	missense_variant	Exon 1 of 2	1		ENSP00000384962.3	Q9UDW1-2
ENSG00000287967	ENST00000668996.1 link	n.544T>C		non_coding_transcript_exon_variant	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000137

AC:

AN:

249054

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000709

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000890

AC:

130

AN:

1461200

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000615

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25A>G (p.K9E) alteration is located in exon 1 (coding exon 1) of the UQCR10 gene. This alteration results from a A to G substitution at nucleotide position 25, causing the lysine (K) at amino acid position 9 to be replaced by a glutamic acid (E). 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

0.20

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.0037

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.049

Sift

Benign

0.77

T;T

Sift4G

Benign

0.96

T;T

Polyphen

0.15

B;B

Vest4

0.20

MVP

0.072

MPC

0.45

ClinPred

0.025

GERP RS

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.48

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over