rs8100724

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006003.3(UQCRFS1):c.16T>G(p.Ser6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,110 control chromosomes in the GnomAD database, including 65,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65583 hom., cov: 36)

Exomes 𝑓: 0.92 ( 580235 hom. )

Failed GnomAD Quality Control

Consequence

UQCRFS1
NM_006003.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.661

Publications

33 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0898138E-6).

BP6

Variant 19-29213103-A-C is Benign according to our data. Variant chr19-29213103-A-C is described in ClinVar as Benign. ClinVar VariationId is 1684192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

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.16T>G	p.Ser6Ala	missense	Exon 1 of 2	NP_005994.2	P47985
UQCRFS1-DT	NR_184021.1		n.-150A>C		upstream_gene	N/A
UQCRFS1-DT	NR_184022.1		n.-150A>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.16T>G	p.Ser6Ala	missense	Exon 1 of 2	ENSP00000306397.3	P47985
UQCRFS1	ENST00000933914.1		c.16T>G	p.Ser6Ala	missense	Exon 1 of 2	ENSP00000603973.1
UQCRFS1-DT	ENST00000587859.2	TSL:2	n.-105A>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.928

AC:

141118

AN:

151998

Hom.:

65530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.934

Gnomad AMI

AF:

0.892

Gnomad AMR

AF:

0.927

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.966

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.920

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.920

GnomAD2 exomes

AF:

0.932

AC:

101723

AN:

109136

AF XY:

0.932

show subpopulations

Gnomad AFR exome

AF:

0.885

Gnomad AMR exome

AF:

0.945

Gnomad ASJ exome

AF:

0.906

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.935

Gnomad NFE exome

AF:

0.910

Gnomad OTH exome

AF:

0.912

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.923

AC:

1256870

AN:

1362224

Hom.:

580235

Cov.:

AF XY:

0.923

AC XY:

620649

AN XY:

672332

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.934

AC:

26569

AN:

28440

American (AMR)

AF:

0.942

AC:

32105

AN:

34080

Ashkenazi Jewish (ASJ)

AF:

0.908

AC:

22084

AN:

24310

East Asian (EAS)

AF:

1.00

AC:

32652

AN:

32660

South Asian (SAS)

AF:

0.954

AC:

74755

AN:

78342

European-Finnish (FIN)

AF:

0.930

AC:

30954

AN:

33266

Middle Eastern (MID)

AF:

0.898

AC:

4172

AN:

4646

European-Non Finnish (NFE)

AF:

0.917

AC:

981092

AN:

1069634

Other (OTH)

AF:

0.923

AC:

52487

AN:

56846

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.394

Heterozygous variant carriers

4783

9565

14348

19130

23913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21022

42044

63066

84088

105110

<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

AF:

0.928

AC:

141226

AN:

152110

Hom.:

65583

Cov.:

AF XY:

0.930

AC XY:

69156

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.934

AC:

38795

AN:

41528

American (AMR)

AF:

0.927

AC:

14177

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

3149

AN:

3470

East Asian (EAS)

AF:

0.999

AC:

5153

AN:

5156

South Asian (SAS)

AF:

0.966

AC:

4665

AN:

4830

European-Finnish (FIN)

AF:

0.938

AC:

9943

AN:

10596

Middle Eastern (MID)

AF:

0.918

AC:

268

AN:

292

European-Non Finnish (NFE)

AF:

0.918

AC:

62319

AN:

67922

Other (OTH)

AF:

0.922

AC:

1949

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

543

1086

1628

2171

2714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.920

Hom.:

121974

Bravo

AF:

0.926

TwinsUK

AF:

0.929

AC:

3443

ALSPAC

AF:

0.922

AC:

3554

ExAC

AF:

0.871

AC:

12866

Asia WGS

AF:

0.980

AC:

3410

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mitochondrial complex III deficiency, nuclear type 10 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.73

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.11

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.024

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.8

PhyloP100

0.66

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.45

REVEL

Benign

0.051

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.013

MPC

0.89

ClinPred

0.0022

GERP RS

-0.080

PromoterAI

0.18

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.27

Mutation Taster

=99/1

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over