Genetic Variant NM_006003.3:c.16T>C (chr19-29213103-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006003.3(UQCRFS1):c.16T>C(p.Ser6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S6A) has been classified as Benign.

Frequency

Genomes: not found (cov: 36)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UQCRFS1
NM_006003.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1286535).

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>C	p.Ser6Pro	missense	Exon 1 of 2	NP_005994.2	P47985
UQCRFS1-DT	NR_184021.1		n.-150A>G		upstream_gene	N/A
UQCRFS1-DT	NR_184022.1		n.-150A>G		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>C	p.Ser6Pro	missense	Exon 1 of 2	ENSP00000306397.3	P47985
UQCRFS1	ENST00000933914.1		c.16T>C	p.Ser6Pro	missense	Exon 1 of 2	ENSP00000603973.1
UQCRFS1-DT	ENST00000587859.2	TSL:2	n.-105A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000220

AC:

AN:

1363846

Hom.:

Cov.:

AF XY:

0.00000297

AC XY:

AN XY:

673084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28500

American (AMR)

AF:

0.00

AC:

AN:

34156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24352

East Asian (EAS)

AF:

0.00

AC:

AN:

32660

South Asian (SAS)

AF:

0.00

AC:

AN:

78406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4680

European-Non Finnish (NFE)

AF:

0.00000280

AC:

AN:

1070884

Other (OTH)

AF:

0.00

AC:

AN:

56924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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.:

Alfa

AF:

0.00

Hom.:

121974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.18

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.33

M_CAP

Benign

0.059

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.66

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.7

REVEL

Benign

0.064

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.059

Polyphen

0.051

Vest4

0.090

MutPred

0.49

Loss of phosphorylation at S6 (P = 0.0309)

MVP

0.15

MPC

1.5

ClinPred

0.61

GERP RS

-0.080

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.76

gMVP

0.50

Mutation Taster

=76/24

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

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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