Variant 5-132866847-C-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 ENST00000378665.1(UQCRQ):c.-35C>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 0.0143 in 1,610,612 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 29 hom., cov: 33)

Exomes 𝑓: 0.014 ( 227 hom. )

Consequence

UQCRQ
ENST00000378665.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.145

Variant links:

Genes affected

UQCRQ (HGNC:29594): (ubiquinol-cytochrome c reductase complex III subunit VII) This gene encodes a ubiquinone-binding protein of low molecular mass. This protein is a small core-associated protein and a subunit of ubiquinol-cytochrome c reductase complex III, which is part of the mitochondrial respiratory chain. [provided by RefSeq, Jul 2008]

UQCRQ links:

GDF9 (HGNC:4224): (growth differentiation factor 9) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates ovarian function. Reduced expression of this gene may be associated with polycystic ovary syndrome and mutations in this gene may be more common in mothers of dizygotic twins. [provided by RefSeq, Jul 2016]

GDF9 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=-0.78).

BP6

Variant 5-132866847-C-T is Benign according to our data. Variant chr5-132866847-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1318354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.013 (1975/152368) while in subpopulation AMR AF= 0.0435 (666/15312). AF 95% confidence interval is 0.0408. There are 29 homozygotes in gnomad4. There are 946 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRQ	NM_014402.5 linkuse as main transcript	c.-13-22C>T		intron_variant		ENST00000378670.8	NP_055217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRQ	ENST00000378670.8 linkuse as main transcript	c.-13-22C>T		intron_variant		1	NM_014402.5	ENSP00000367939	P1

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1974

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0434

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0133

AC:

3294

AN:

247398

Hom.:

AF XY:

0.0120

AC XY:

1613

AN XY:

134490

show subpopulations

Gnomad AFR exome

AF:

0.00289

Gnomad AMR exome

AF:

0.0366

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00350

Gnomad FIN exome

AF:

0.00514

Gnomad NFE exome

AF:

0.0140

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0144

AC:

21023

AN:

1458244

Hom.:

227

Cov.:

AF XY:

0.0137

AC XY:

9951

AN XY:

725552

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.0402

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00339

Gnomad4 FIN exome

AF:

0.00472

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0130

AC:

1975

AN:

152368

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

946

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.0435

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00463

Hom.:

Bravo

AF:

0.0147

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.5

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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