rs30177

Positions:

• chr5-132866719-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000378665.1(UQCRQ):​c.-163C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 880,142 control chromosomes in the GnomAD database, including 225,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (39135 hom., cov: 33)
  • Exomes 𝑓: 0.71 (186547 hom.)
• Consequence: UQCRQ ENST00000378665.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.676

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-132866719-C-G is Benign according to our data. Variant chr5-132866719-C-G is described in ClinVar as [Benign]. Clinvar id is 1225029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRQ	NM_014402.5	c.-14+32C>G		intron_variant		ENST00000378670.8	NP_055217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRQ	ENST00000378670.8	c.-14+32C>G		intron_variant		1	NM_014402.5	ENSP00000367939	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108291 AN: 151968 Hom.: 39099 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.712

GnomAD4 exome AF: 0.711 AC: 517616 AN: 728056 Hom.: 186547 Cov.: 9 AF XY: 0.712 AC XY: 266583 AN XY: 374586

Gnomad4 AFR exome AF: 0.767

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.740

Gnomad4 OTH exome AF: 0.708

GnomAD4 genome AF: 0.713 AC: 108381 AN: 152086 Hom.: 39135 Cov.: 33 AF XY: 0.704 AC XY: 52298 AN XY: 74334

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.713

Alfa AF: 0.718 Hom.: 4894

Bravo AF: 0.717

Asia WGS AF: 0.571 AC: 1988 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs30177; hg19: chr5-132202411;