chr5-132866719-C-T

Variant names:

• chr5-132866719-C-T
• rs30177
• ENST00000378665.1:c.-163C>T

Variant summary

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

The ENST00000378665.1(UQCRQ):​c.-163C>T 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 0.00000274 in 729,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UQCRQ ENST00000378665.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• Publications: 0 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=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378665.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRQ	NM_014402.5	MANE Select	c.-14+32C>T		intron	N/A	NP_055217.2
	GDF9	NM_005260.7	MANE Select	c.-2186G>A		upstream_gene	N/A	NP_005251.1
	GDF9	NM_001288824.4		c.-152G>A		upstream_gene	N/A	NP_001275753.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRQ	ENST00000378665.1	TSL:1	c.-163C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000367934.1
	UQCRQ	ENST00000378665.1	TSL:1	c.-163C>T		5_prime_UTR	Exon 1 of 2	ENSP00000367934.1
	UQCRQ	ENST00000378670.8	TSL:1 MANE Select	c.-14+32C>T		intron	N/A	ENSP00000367939.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 2 AN: 729218 Hom.: 0 Cov.: 9 AF XY: 0.00000533 AC XY: 2 AN XY: 375182

African (AFR) AF: 0.00 AC: 0 AN: 18526

American (AMR) AF: 0.00 AC: 0 AN: 28186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17326

East Asian (EAS) AF: 0.00 AC: 0 AN: 32582

South Asian (SAS) AF: 0.0000348 AC: 2 AN: 57520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 506000

Other (OTH) AF: 0.00 AC: 0 AN: 35672

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.92
PhyloP100		0.68
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs30177; hg19: chr5-132202411;