Genetic Variant UQCRQ:c.-175T>A (chr5-132866707-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.852

Publications

15 publications found

Variant links:

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]

UQCRQ links:

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)

GDF9 links:

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ACMG classification

Classification was made for transcript

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).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UQCRQ	NM_014402.5	MANE Select	c.-14+20T>A	intron	N/A	NP_055217.2	O14949
GDF9	NM_005260.7	MANE Select	c.-2174A>T	upstream_gene	N/A	NP_005251.1	O60383
GDF9	NM_001288824.4		c.-140A>T	upstream_gene	N/A	NP_001275753.1	B4DXG3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UQCRQ	ENST00000378665.1	TSL:1	c.-175T>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000367934.1	O14949
UQCRQ	ENST00000378665.1	TSL:1	c.-175T>A	5_prime_UTR	Exon 1 of 2	ENSP00000367934.1	O14949
UQCRQ	ENST00000378670.8	TSL:1 MANE Select	c.-14+20T>A	intron	N/A	ENSP00000367939.3	O14949

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

596458

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

310326

African (AFR)

AF:

0.00

AC:

AN:

15666

American (AMR)

AF:

0.00

AC:

AN:

24292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15536

East Asian (EAS)

AF:

0.00

AC:

AN:

31900

South Asian (SAS)

AF:

0.00

AC:

AN:

52566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2332

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

392992

Other (OTH)

AF:

0.00

AC:

AN:

31074

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

5607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.4

(source)

DANN

Benign

0.60

PhyloP100

-0.85

PromoterAI

-0.12

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over