chr16-21965441-G-A

Position:

chr16-21965441-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1

The NM_003366.4(UQCRC2):c.548G>A(p.Arg183Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,613,620 control chromosomes in the GnomAD database, including 2,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183W) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.037 ( 156 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2035 hom. )

Consequence

UQCRC2
NM_003366.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

UQCRC2 (HGNC:12586): (ubiquinol-cytochrome c reductase core protein 2) The protein encoded by this gene is located in the mitochondrion, where it is part of the ubiquinol-cytochrome c reductase complex (also known as complex III). This complex constitutes a part of the mitochondrial respiratory chain. Defects in this gene are a cause of mitochondrial complex III deficiency nuclear type 5. [provided by RefSeq, Jul 2015]

UQCRC2 links:

PDZD9 (HGNC:):

PDZD9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr16-21965440-C-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.0042624474).

BP6

Variant 16-21965441-G-A is Benign according to our data. Variant chr16-21965441-G-A is described in ClinVar as [Benign]. Clinvar id is 380582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21965441-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UQCRC2	NM_003366.4 linkuse as main transcript	c.548G>A	p.Arg183Gln	missense_variant	7/14	ENST00000268379.9	NP_003357.2
PDZD9	XM_017023109.2 linkuse as main transcript	c.607-7824C>T		intron_variant			XP_016878598.1
PDZD9	XM_047433888.1 linkuse as main transcript	c.601-7824C>T		intron_variant			XP_047289844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRC2	ENST00000268379.9 linkuse as main transcript	c.548G>A	p.Arg183Gln	missense_variant	7/14	1	NM_003366.4	ENSP00000268379	P1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5605

AN:

152076

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00985

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0319

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.0548

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0278

GnomAD3 exomes

AF:

0.0393

AC:

9863

AN:

250954

Hom.:

273

AF XY:

0.0394

AC XY:

5349

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.0535

Gnomad NFE exome

AF:

0.0615

Gnomad OTH exome

AF:

0.0437

GnomAD4 exome

AF:

0.0480

AC:

70150

AN:

1461424

Hom.:

2035

Cov.:

AF XY:

0.0473

AC XY:

34384

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00828

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0130

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.0553

Gnomad4 OTH exome

AF:

0.0395

GnomAD4 genome

AF:

0.0368

AC:

5602

AN:

152196

Hom.:

156

Cov.:

AF XY:

0.0364

AC XY:

2711

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00982

Gnomad4 AMR

AF:

0.0319

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00993

Gnomad4 FIN

AF:

0.0548

Gnomad4 NFE

AF:

0.0568

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.0494

Hom.:

370

Bravo

AF:

0.0341

TwinsUK

AF:

0.0518

AC:

192

ALSPAC

AF:

0.0522

AC:

201

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0537

AC:

462

ExAC

AF:

0.0429

AC:

5207

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 12, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mitochondrial complex III deficiency nuclear type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.76

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.085

Sift

Uncertain

0.024

D;D;D

Sift4G

Benign

0.074

T;T;T

Polyphen

0.59

P;.;.

Vest4

0.061

MPC

0.48

ClinPred

0.026

GERP RS

1.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.36

gMVP

0.52

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

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