Variant 11-62672055-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001085372.3(UQCC3):c.223G>T(p.Ala75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UQCC3
NM_001085372.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCC3	NM_001085372.3 linkuse as main transcript	c.223G>T	p.Ala75Ser	missense_variant	2/2	ENST00000377953.4	NP_001078841.1	Q6UW78
LBHD1	NM_024099.5 linkuse as main transcript	c.-502C>A		5_prime_UTR_variant	1/7	ENST00000354588.8	NP_077004.2	Q9BQE6-2A0A024R584

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UQCC3	ENST00000377953.4 linkuse as main transcript	c.223G>T	p.Ala75Ser	missense_variant	2/2	1	NM_001085372.3	ENSP00000367189.3	Q6UW78
LBHD1	ENST00000354588.8 linkuse as main transcript	c.-502C>A		5_prime_UTR_variant	1/7	1	NM_024099.5	ENSP00000346600.3	Q9BQE6-2
UQCC3	ENST00000531323.1 linkuse as main transcript	c.223G>T	p.Ala75Ser	missense_variant	3/3	3		ENSP00000432692.1	Q6UW78
LBHD1	ENST00000528862.2 linkuse as main transcript	c.93+72C>A		intron_variant		3		ENSP00000434489.2	E9PQ29

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724740

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 28, 2022

The c.223G>T (p.A75S) alteration is located in exon 2 (coding exon 2) of the UQCC3 gene. This alteration results from a G to T substitution at nucleotide position 223, causing the alanine (A) at amino acid position 75 to be replaced by a serine (S). 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

0.0012

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.69

D;D

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.67

.;T

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.64

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.016

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.95

P;P

Vest4

0.41

MutPred

0.16

Gain of disorder (P = 0.0587);Gain of disorder (P = 0.0587);

MVP

0.29

MPC

0.73

ClinPred

0.99

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.086

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.

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