Variant 19-29213082-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006003.3(UQCRFS1):c.37C>G(p.Pro13Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000744 in 1,343,294 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

UQCRFS1
NM_006003.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

UQCRFS1 (HGNC:12587): (ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1) Predicted to enable oxidoreductase activity. Involved in mitochondrial respiratory chain complex III assembly and respiratory electron transport chain. Located in mitochondrion. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. Implicated in mitochondrial complex III deficiency. [provided by Alliance of Genome Resources, Apr 2022]

UQCRFS1 links:

UQCRFS1-DT (HGNC:55295): (UQCRFS1 divergent transcript)

UQCRFS1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRFS1	NM_006003.3 link	c.37C>G	p.Pro13Ala	missense_variant	Exon 1 of 2	ENST00000304863.6	NP_005994.2	P47985
UQCRFS1-DT	NR_184021.1 link	n.-171G>C		upstream_gene_variant
UQCRFS1-DT	NR_184022.1 link	n.-171G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UQCRFS1	ENST00000304863.6 link	c.37C>G	p.Pro13Ala	missense_variant	Exon 1 of 2	1	NM_006003.3	ENSP00000306397.3	P47985
UQCRFS1-DT	ENST00000587859.1 link	n.-153G>C		upstream_gene_variant		2
UQCRFS1-DT	ENST00000590607.2 link	n.-201G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.44e-7

AC:

AN:

1343294

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

662518

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:

9.41e-7

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

Jan 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37C>G (p.P13A) alteration is located in exon 1 (coding exon 1) of the UQCRFS1 gene. This alteration results from a C to G substitution at nucleotide position 37, causing the proline (P) at amino acid position 13 to be replaced by an alanine (A). 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

0.064

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.68

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.032

Polyphen

0.71

Vest4

0.32

MutPred

0.69

Gain of helix (P = 0.0117);

MVP

0.60

MPC

2.2

ClinPred

0.98

GERP RS

4.4

Varity_R

0.90

gMVP

0.48

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