Genetic Variant NM_006294.5:c.19G>T (chr8-96235512-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006294.5(UQCRB):c.19G>T(p.Val7Phe) variant causes a missense, splice region 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. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

UQCRB
NM_006294.5 missense, splice_region

Scores

Splicing: ADA: 0.9997

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Publications

0 publications found

Variant links:

Genes affected

UQCRB (HGNC:12582): (ubiquinol-cytochrome c reductase binding protein) This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. This protein plays an important role in hypoxia-induced angiogenesis through mitochondrial reactive oxygen species-mediated signaling. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X. [provided by RefSeq, Dec 2011]

UQCRB links:

UQCRB-AS1 (HGNC:55521): (UQCRB antisense RNA 1)

UQCRB-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006294.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UQCRB	NM_006294.5	MANE Select	c.19G>T	p.Val7Phe	missense splice_region	Exon 1 of 4	NP_006285.1	P14927-1
UQCRB	NM_001254752.2		c.19G>T	p.Val7Phe	missense splice_region	Exon 1 of 5	NP_001241681.1	P14927-2
UQCRB	NM_001199975.3		c.-192G>T		splice_region	Exon 1 of 5	NP_001186904.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UQCRB	ENST00000287022.10	TSL:1 MANE Select	c.19G>T	p.Val7Phe	missense splice_region	Exon 1 of 4	ENSP00000287022.5	P14927-1
UQCRB	ENST00000517603.5	TSL:1	n.19G>T		splice_region non_coding_transcript_exon	Exon 1 of 5	ENSP00000430672.1	E5RIT7
UQCRB	ENST00000518876.1	TSL:1	n.33G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.72

M_CAP

Benign

0.021

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.5

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Benign

0.043

Sift4G

Benign

0.14

Polyphen

0.071

Vest4

0.47

MutPred

0.47

Loss of MoRF binding (P = 0.0814)

MVP

0.32

MPC

0.49

ClinPred

0.95

GERP RS

3.3

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.64

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.11

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