Genetic Variant NM_006003.3:c.37C>G (chr19-29213082-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006003.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UQCRFS1	NM_006003.3	MANE Select	c.37C>G	p.Pro13Ala	missense	Exon 1 of 2	NP_005994.2	P47985
UQCRFS1-DT	NR_184021.1		n.-171G>C		upstream_gene	N/A
UQCRFS1-DT	NR_184022.1		n.-171G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UQCRFS1	ENST00000304863.6	TSL:1 MANE Select	c.37C>G	p.Pro13Ala	missense	Exon 1 of 2	ENSP00000306397.3	P47985
UQCRFS1	ENST00000933914.1		c.37C>G	p.Pro13Ala	missense	Exon 1 of 2	ENSP00000603973.1
UQCRFS1-DT	ENST00000587859.2	TSL:2	n.-126G>C		upstream_gene	N/A

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

African (AFR)

AF:

0.00

AC:

AN:

27062

American (AMR)

AF:

0.00

AC:

AN:

30126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23472

East Asian (EAS)

AF:

0.00

AC:

AN:

30342

South Asian (SAS)

AF:

0.00

AC:

AN:

75610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4614

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1063130

Other (OTH)

AF:

0.00

AC:

AN:

56006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

0.064

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

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

PhyloP100

5.2

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

PromoterAI

0.027

Neutral

(source)

Varity_R

0.90

gMVP

0.48

Mutation Taster

=53/47

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over