5-132866719-C-G

Variant names:

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

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.-163C>G 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 0.711 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_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.676
• 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=-0.87).
• BP6: Variant 5-132866719-C-G is Benign according to our data. Variant chr5-132866719-C-G is described in ClinVar as Benign. ClinVar VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRQ	NM_014402.5	MANE Select	c.-14+32C>G		intron	N/A	NP_055217.2	O14949
	GDF9	NM_005260.7	MANE Select	c.-2186G>C		upstream_gene	N/A	NP_005251.1	O60383
	GDF9	NM_001288824.4		c.-152G>C		upstream_gene	N/A	NP_001275753.1	B4DXG3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRQ	ENST00000378665.1	TSL:1	c.-163C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000367934.1	O14949
	UQCRQ	ENST00000378665.1	TSL:1	c.-163C>G		5_prime_UTR	Exon 1 of 2	ENSP00000367934.1	O14949
	UQCRQ	ENST00000378670.8	TSL:1 MANE Select	c.-14+32C>G		intron	N/A	ENSP00000367939.3	O14949

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

African (AFR) AF: 0.767 AC: 14190 AN: 18504

American (AMR) AF: 0.576 AC: 16197 AN: 28140

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 13524 AN: 17316

East Asian (EAS) AF: 0.459 AC: 14949 AN: 32564

South Asian (SAS) AF: 0.696 AC: 40033 AN: 57486

European-Finnish (FIN) AF: 0.576 AC: 17707 AN: 30754

Middle Eastern (MID) AF: 0.729 AC: 1929 AN: 2646

European-Non Finnish (NFE) AF: 0.740 AC: 373870 AN: 505028

Other (OTH) AF: 0.708 AC: 25217 AN: 35618

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

African (AFR) AF: 0.754 AC: 31292 AN: 41508

American (AMR) AF: 0.669 AC: 10227 AN: 15290

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

East Asian (EAS) AF: 0.433 AC: 2224 AN: 5134

South Asian (SAS) AF: 0.674 AC: 3255 AN: 4826

European-Finnish (FIN) AF: 0.576 AC: 6088 AN: 10566

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

European-Non Finnish (NFE) AF: 0.737 AC: 50125 AN: 67972

Other (OTH) AF: 0.713 AC: 1506 AN: 2112

Alfa AF: 0.718 Hom.: 4894

Bravo AF: 0.717

Asia WGS AF: 0.571 AC: 1988 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.45
PhyloP100		0.68
PromoterAI		-0.042	Neutral
Mutation Taster		=297/3	polymorphism (auto)

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;