chr5-132866707-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000378665.1(UQCRQ):​c.-175T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UQCRQ ENST00000378665.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRQ	NM_014402.5	c.-14+20T>A		intron_variant	Intron 1 of 2	ENST00000378670.8	NP_055217.2
GDF9	NM_005260.7	c.-2174A>T		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>A		intron_variant	Intron 1 of 2	1	NM_014402.5	ENSP00000367939.3
GDF9	ENST00000687138.1	c.-2174A>T		upstream_gene_variant			NM_005260.7	ENSP00000510441.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 596458 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 310326

African (AFR) AF: 0.00 AC: 0 AN: 15666

American (AMR) AF: 0.00 AC: 0 AN: 24292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15536

East Asian (EAS) AF: 0.00 AC: 0 AN: 31900

South Asian (SAS) AF: 0.00 AC: 0 AN: 52566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 392992

Other (OTH) AF: 0.00 AC: 0 AN: 31074

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 5607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-0.85
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs30178; hg19: chr5-132202399;