chr16-88706555-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012759.3(CTU2):c.25G>C(p.Gly9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CTU2
NM_001012759.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Publications

5 publications found

Variant links:

Genes affected

CTU2 (HGNC:28005): (cytosolic thiouridylase subunit 2) This gene encodes a protein which is involved in the post-transcriptional modification of transfer RNAs (tRNAs). The encoded protein plays a role in thiolation of uridine residue present at the wobble position in a subset of tRNAs, resulting in enhanced codon reading accuracy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

CTU2 links:

RNF166 (HGNC:28856): (ring finger protein 166) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNF166 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031057984).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012759.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTU2	NM_001012759.3	MANE Select	c.25G>C	p.Gly9Arg	missense	Exon 1 of 15	NP_001012777.1	Q2VPK5-1
CTU2	NM_001318507.2		c.25G>C	p.Gly9Arg	missense	Exon 1 of 15	NP_001305436.1	H3BSW6
CTU2	NM_001012762.3		c.25G>C	p.Gly9Arg	missense	Exon 1 of 14	NP_001012780.1	Q2VPK5-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTU2	ENST00000453996.7	TSL:1 MANE Select	c.25G>C	p.Gly9Arg	missense	Exon 1 of 15	ENSP00000388320.2	Q2VPK5-1
CTU2	ENST00000567949.5	TSL:1	c.25G>C	p.Gly9Arg	missense	Exon 1 of 15	ENSP00000456908.1	H3BSW6
CTU2	ENST00000564105.5	TSL:1	n.25G>C		non_coding_transcript_exon	Exon 1 of 14	ENSP00000454923.1	H3BNM3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1306566

Hom.:

Cov.:

AF XY:

0.00000310

AC XY:

AN XY:

644522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26132

American (AMR)

AF:

0.00

AC:

AN:

23248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22794

East Asian (EAS)

AF:

0.00

AC:

AN:

28144

South Asian (SAS)

AF:

0.0000140

AC:

AN:

71358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3926

European-Non Finnish (NFE)

AF:

9.58e-7

AC:

AN:

1044230

Other (OTH)

AF:

0.00

AC:

AN:

54044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

AF:

0.0000132

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0053

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.67

M_CAP

Benign

0.027

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.61

PhyloP100

-0.79

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.5

REVEL

Benign

0.028

Sift

Benign

0.41

Sift4G

Benign

0.14

Polyphen

0.0030

Vest4

0.015

MutPred

0.10

Loss of relative solvent accessibility (P = 0.0676)

MVP

0.17

ClinPred

0.062

GERP RS

1.1

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.077

gMVP

0.29

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over