Variant 11-62672062-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000377953.4(UQCC3):c.230G>A(p.Arg77Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,456,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

UQCC3
ENST00000377953.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

Variant links:

Genes affected

UQCC3 (HGNC:34399): (ubiquinol-cytochrome c reductase complex assembly factor 3) Complex III is a mitochondrial inner membrane protein complex that transfers electrons from ubiquinol to cytochrome c. This gene encodes a protein that functions in complex III assembly. Mutations in this gene result in Mitochondrial complex III deficiency, nuclear type 9. [provided by RefSeq, Dec 2014]

UQCC3 links:

LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

LBHD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37869763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCC3	NM_001085372.3 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	2/2	ENST00000377953.4	NP_001078841.1
LBHD1	NM_024099.5 linkuse as main transcript	c.-509C>T		5_prime_UTR_variant	1/7	ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCC3	ENST00000377953.4 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	2/2	1	NM_001085372.3	ENSP00000367189	P1
LBHD1	ENST00000354588.8 linkuse as main transcript	c.-509C>T		5_prime_UTR_variant	1/7	1	NM_024099.5	ENSP00000346600	P1	Q9BQE6-2
UQCC3	ENST00000531323.1 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	3/3	3		ENSP00000432692	P1
LBHD1	ENST00000528862.2 linkuse as main transcript	c.93+65C>T		intron_variant		3		ENSP00000434489

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000861

AC:

AN:

232328

Hom.:

AF XY:

0.00000789

AC XY:

AN XY:

126730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000117

Gnomad SAS 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:

0.00000412

AC:

AN:

1456126

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

723908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.230G>A (p.R77K) alteration is located in exon 2 (coding exon 2) of the UQCC3 gene. This alteration results from a G to A substitution at nucleotide position 230, causing the arginine (R) at amino acid position 77 to be replaced by a lysine (K). 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

0.33

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.76

MutationTaster

Benign

0.94

N;N

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.51

MutPred

0.35

Gain of methylation at R77 (P = 0.0046);Gain of methylation at R77 (P = 0.0046);

MVP

0.21

MPC

0.46

ClinPred

0.99

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.81

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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