5-132866707-T-C

Variant names:

• chr5-132866707-T-C
• rs30178
• ENST00000378665.1:c.-175T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000378665.1(UQCRQ):​c.-175T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 747,666 control chromosomes in the GnomAD database, including 189,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (39138 hom., cov: 32)
  • Exomes 𝑓: 0.70 (150089 hom.)
• Consequence: UQCRQ ENST00000378665.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.852
• Publications: 15 publications found

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]

GDF9 Gene-Disease associations (from GenCC):

• premature ovarian failure 14

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-132866707-T-C is Benign according to our data. Variant chr5-132866707-T-C is described in ClinVar as [Benign]. Clinvar id is 1183892.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 rank	MANE	Protein	UniProt
UQCRQ	NM_014402.5	c.-14+20T>C		intron_variant	Intron 1 of 2	ENST00000378670.8	NP_055217.2
GDF9	NM_005260.7	c.-2174A>G		upstream_gene_variant		ENST00000687138.1	NP_005251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCRQ	ENST00000378670.8	c.-14+20T>C		intron_variant	Intron 1 of 2	1	NM_014402.5	ENSP00000367939.3
GDF9	ENST00000687138.1	c.-2174A>G		upstream_gene_variant			NM_005260.7	ENSP00000510441.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108295 AN: 151954 Hom.: 39101 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.712

GnomAD4 exome AF: 0.705 AC: 419726 AN: 595594 Hom.: 150089 Cov.: 8 AF XY: 0.706 AC XY: 218632 AN XY: 309862

African (AFR) AF: 0.766 AC: 11979 AN: 15634

American (AMR) AF: 0.578 AC: 14006 AN: 24236

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 12063 AN: 15518

East Asian (EAS) AF: 0.459 AC: 14625 AN: 31868

South Asian (SAS) AF: 0.694 AC: 36476 AN: 52546

European-Finnish (FIN) AF: 0.575 AC: 17292 AN: 30078

Middle Eastern (MID) AF: 0.722 AC: 1684 AN: 2332

European-Non Finnish (NFE) AF: 0.738 AC: 289682 AN: 392358

Other (OTH) AF: 0.707 AC: 21919 AN: 31024

GnomAD4 genome AF: 0.713 AC: 108386 AN: 152072 Hom.: 39138 Cov.: 32 AF XY: 0.704 AC XY: 52303 AN XY: 74322

African (AFR) AF: 0.754 AC: 31301 AN: 41506

American (AMR) AF: 0.669 AC: 10223 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2693 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2225 AN: 5130

South Asian (SAS) AF: 0.675 AC: 3258 AN: 4824

European-Finnish (FIN) AF: 0.576 AC: 6085 AN: 10558

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50123 AN: 67980

Other (OTH) AF: 0.713 AC: 1507 AN: 2114

Alfa AF: 0.717 Hom.: 5607

Bravo AF: 0.717

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.61
PhyloP100		-0.85
PromoterAI		-0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs30178; hg19: chr5-132202399;