Variant chr16-21953392-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003366.4(UQCRC2):c.-32G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,610,950 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 24 hom. )

Consequence

UQCRC2
NM_003366.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.21

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-21953392-G-T is Benign according to our data. Variant chr16-21953392-G-T is described in ClinVar as [Benign]. Clinvar id is 385674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000874 (133/152224) while in subpopulation SAS AF= 0.017 (82/4812). AF 95% confidence interval is 0.0141. There are 4 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRC2	NM_003366.4 linkuse as main transcript	c.-32G>T		5_prime_UTR_variant	1/14	ENST00000268379.9	NP_003357.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRC2	ENST00000268379.9 linkuse as main transcript	c.-32G>T		5_prime_UTR_variant	1/14	1	NM_003366.4	ENSP00000268379	P1

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

134

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00189

AC:

465

AN:

245940

Hom.:

AF XY:

0.00256

AC XY:

340

AN XY:

132756

show subpopulations

Gnomad AFR exome

AF:

0.0000640

Gnomad AMR exome

AF:

0.0000881

Gnomad ASJ exome

AF:

0.00193

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000610

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00119

AC:

1729

AN:

1458726

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1131

AN XY:

725258

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00139

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000414

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.000874

AC:

133

AN:

152224

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00100

Hom.:

Bravo

AF:

0.000389

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 03, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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