Variant chr1-46310228-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006004.4(UQCRH):c.155T>G(p.Leu52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UQCRH
NM_006004.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0330

Variant links:

Genes affected

UQCRH (HGNC:12590): (ubiquinol-cytochrome c reductase hinge protein) Predicted to enable ubiquinol-cytochrome-c reductase activity. Predicted to be involved in mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

UQCRH links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35333502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UQCRH	NM_006004.4 linkuse as main transcript	c.155T>G	p.Leu52Arg	missense_variant	3/4	ENST00000311672.10
UQCRH	NM_001297565.2 linkuse as main transcript	c.137T>G	p.Leu46Arg	missense_variant	4/5
UQCRH	NM_001297566.2 linkuse as main transcript	c.128T>G	p.Leu43Arg	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
UQCRH	ENST00000311672.10 linkuse as main transcript	c.155T>G	p.Leu52Arg	missense_variant	3/4	1	NM_006004.4	P1
UQCRH	ENST00000496387.5 linkuse as main transcript	c.303T>G	p.Ala101=	synonymous_variant, NMD_transcript_variant	4/5	1
UQCRH	ENST00000460947.1 linkuse as main transcript	n.308T>G		non_coding_transcript_exon_variant	1/2	2
UQCRH	ENST00000489056.5 linkuse as main transcript	c.171T>G	p.Ala57=	synonymous_variant, NMD_transcript_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.155T>G (p.L52R) alteration is located in exon 3 (coding exon 3) of the UQCRH gene. This alteration results from a T to G substitution at nucleotide position 155, causing the leucine (L) at amino acid position 52 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.71

M_CAP

Benign

0.0080

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.82

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Benign

0.49

Sift4G

Benign

0.48

Polyphen

0.25

Vest4

0.64

MutPred

0.47

Gain of MoRF binding (P = 0.0063);

MVP

0.085

MPC

0.45

ClinPred

0.62

GERP RS

2.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.31

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over