Genetic Variant UQCC1:p.Arg51Leu (chr20-35384111-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018244.5(UQCC1):c.152G>T(p.Arg51Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R51Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UQCC1
NM_018244.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.150

Publications

78 publications found

Variant links:

Genes affected

UQCC1 (HGNC:15891): (ubiquinol-cytochrome c reductase complex assembly factor 1) This gene encodes a transmembrane protein that is structurally similar to the mouse basic fibroblast growth factor repressed ZIC-binding protein. In mouse this protein may be involved in fibroblast growth factor regulated growth control. In humans, polymorphisms in this gene are associated with variation in human height and osteoarthritis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

UQCC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051528484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCC1	NM_018244.5 link	c.152G>T	p.Arg51Leu	missense_variant	Exon 3 of 10	ENST00000374385.10	NP_060714.3	Q9NVA1-1Q3KRB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCC1	ENST00000374385.10 link	c.152G>T	p.Arg51Leu	missense_variant	Exon 3 of 10	1	NM_018244.5	ENSP00000363506.5		Q9NVA1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726488

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110836

Other (OTH)

AF:

0.00

AC:

AN:

60312

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.14

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.025

.;T;.;T;T;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0081

LIST_S2

Benign

0.48

T;T;T;T;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.052

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

N;.;N;N;.;.;.

PhyloP100

-0.15

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.8

N;N;N;N;.;N;N

REVEL

Benign

0.031

Sift

Benign

0.31

T;T;T;T;.;T;T

Sift4G

Benign

0.21

T;T;T;T;T;.;T

Polyphen

0.0, 0.0010

.;.;.;B;.;.;B

Vest4

0.071

MutPred

0.33

Loss of catalytic residue at R51 (P = 0.0062);Loss of catalytic residue at R51 (P = 0.0062);Loss of catalytic residue at R51 (P = 0.0062);Loss of catalytic residue at R51 (P = 0.0062);.;.;Loss of catalytic residue at R51 (P = 0.0062);

MVP

0.072

MPC

0.36

ClinPred

0.18

GERP RS

-9.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.24

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over