19-29213103-A-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRFS1	NM_006003.3 link	c.16T>G	p.Ser6Ala	missense_variant	Exon 1 of 2	ENST00000304863.6	NP_005994.2	P47985
UQCRFS1-DT	NR_184021.1 link	n.-150A>C		upstream_gene_variant
UQCRFS1-DT	NR_184022.1 link	n.-150A>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UQCRFS1	ENST00000304863.6 link	c.16T>G	p.Ser6Ala	missense_variant	Exon 1 of 2	1	NM_006003.3	ENSP00000306397.3	P47985
UQCRFS1-DT	ENST00000587859.1 link	n.-132A>C		upstream_gene_variant		2
UQCRFS1-DT	ENST00000590607.2 link	n.-180A>C		upstream_gene_variant		3

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

GnomAD3 exomes

AF:

0.932

AC:

101723

AN:

109136

Hom.:

47498

AF XY:

0.932

AC XY:

56697

AN XY:

60804

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 SAS exome

AF:

0.954

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

Gnomad4 AFR exome

AF:

0.934

Gnomad4 AMR exome

AF:

0.942

Gnomad4 ASJ exome

AF:

0.908

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.954

Gnomad4 FIN exome

AF:

0.930

Gnomad4 NFE exome

AF:

0.917

Gnomad4 OTH exome

AF:

0.923

GnomAD4 genome

AF:

0.928

AC:

141226

AN:

152110

Hom.:

65583

Cov.:

AF XY:

0.930

AC XY:

69156

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.934

Gnomad4 AMR

AF:

0.927

Gnomad4 ASJ

AF:

0.907

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.966

Gnomad4 FIN

AF:

0.938

Gnomad4 NFE

AF:

0.918

Gnomad4 OTH

AF:

0.922

Alfa

AF:

0.919

Hom.:

90976

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mitochondrial complex 3 deficiency, nuclear type 10

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.73

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

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

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

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