Genetic Variant UQCC5:p.Arg66Lys (chr3-52540469-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001124767.2(UQCC5):c.197G>A(p.Arg66Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,379,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

UQCC5
NM_001124767.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Publications

0 publications found

Variant links:

Genes affected

UQCC5 (HGNC:37257): (ubiquinol-cytochrome c reductase complex assembly factor 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

UQCC5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14259207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124767.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC5	NM_001124767.2	MANE Select	c.197G>A	p.Arg66Lys	missense	Exon 2 of 2	NP_001118239.1	Q8WVI0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UQCC5	ENST00000477703.6	TSL:1 MANE Select	c.197G>A	p.Arg66Lys	missense	Exon 2 of 2	ENSP00000417806.1	Q8WVI0
UQCC5	ENST00000916170.1		c.197G>A	p.Arg66Lys	missense	Exon 4 of 4	ENSP00000586229.1
UQCC5	ENST00000307106.3	TSL:2	c.64G>A	p.Gly22Ser	missense	Exon 2 of 2	ENSP00000305661.3	F8W7Q2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

136974

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.25e-7

AC:

AN:

1379932

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680240

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30278

American (AMR)

AF:

0.0000345

AC:

AN:

28970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24636

East Asian (EAS)

AF:

0.00

AC:

AN:

35142

South Asian (SAS)

AF:

0.00

AC:

AN:

74296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074494

Other (OTH)

AF:

0.00

AC:

AN:

57274

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.095

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.83

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

PhyloP100

1.9

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.17

Vest4

0.18

MutPred

0.083

Gain of glycosylation at S18 (P = 0.0118)

MVP

0.10

ClinPred

0.94

GERP RS

3.9

Varity_R

0.059

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over