Variant chr1-46303806-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006004.4(UQCRH):c.40G>C(p.Gly14Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UQCRH
NM_006004.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15840304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UQCRH	NM_006004.4 linkuse as main transcript	c.40G>C	p.Gly14Arg	missense_variant	1/4	ENST00000311672.10
UQCRH	NM_001297566.2 linkuse as main transcript	c.40G>C	p.Gly14Arg	missense_variant	1/3
UQCRH	NM_001297565.2 linkuse as main transcript	c.-127G>C		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
UQCRH	ENST00000311672.10 linkuse as main transcript	c.40G>C	p.Gly14Arg	missense_variant	1/4	1	NM_006004.4	P1
UQCRH	ENST00000496387.5 linkuse as main transcript	c.40G>C	p.Gly14Arg	missense_variant, NMD_transcript_variant	1/5	1
UQCRH	ENST00000486951.1 linkuse as main transcript	n.100G>C		non_coding_transcript_exon_variant	1/2	3
UQCRH	ENST00000489056.5 linkuse as main transcript	c.40G>C	p.Gly14Arg	missense_variant, NMD_transcript_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251330

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

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

May 23, 2023

The c.40G>C (p.G14R) alteration is located in exon 1 (coding exon 1) of the UQCRH gene. This alteration results from a G to C substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 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

0.10

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

Eigen

Benign

0.035

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

M_CAP

Benign

0.058

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.4

REVEL

Benign

0.17

Sift

Benign

0.14

Sift4G

Benign

0.066

Polyphen

0.0030

Vest4

0.36

MutPred

0.39

Gain of solvent accessibility (P = 0.0037);

MVP

0.17

MPC

0.37

ClinPred

0.94

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over