16-88706566-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6_ModerateBS1

The NM_001012759.3(CTU2):​c.36G>A​(p.Ala12Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000934 in 1,456,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CTU2
NM_001012759.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.111
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 16-88706566-G-A is Benign according to our data. Variant chr16-88706566-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1668718.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000487 (74/152094) while in subpopulation AFR AF= 0.00166 (69/41524). AF 95% confidence interval is 0.00135. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTU2NM_001012759.3 linkc.36G>A p.Ala12Ala synonymous_variant Exon 1 of 15 ENST00000453996.7 NP_001012777.1 Q2VPK5-1
CTU2NM_001318507.2 linkc.36G>A p.Ala12Ala synonymous_variant Exon 1 of 15 NP_001305436.1 Q2VPK5H3BSW6
CTU2NM_001012762.3 linkc.36G>A p.Ala12Ala synonymous_variant Exon 1 of 14 NP_001012780.1 Q2VPK5-5
CTU2NM_001318513.2 linkc.-147G>A 5_prime_UTR_variant Exon 1 of 14 NP_001305442.1 Q2VPK5-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTU2ENST00000453996.7 linkc.36G>A p.Ala12Ala synonymous_variant Exon 1 of 15 1 NM_001012759.3 ENSP00000388320.2 Q2VPK5-1

Frequencies

GnomAD3 genomes
AF:
0.000487
AC:
74
AN:
151986
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00167
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.0000585
AC:
4
AN:
68406
Hom.:
0
AF XY:
0.0000249
AC XY:
1
AN XY:
40186
show subpopulations
Gnomad AFR exome
AF:
0.00249
Gnomad AMR exome
AF:
0.000166
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000475
AC:
62
AN:
1304672
Hom.:
0
Cov.:
31
AF XY:
0.0000482
AC XY:
31
AN XY:
643532
show subpopulations
Gnomad4 AFR exome
AF:
0.00196
Gnomad4 AMR exome
AF:
0.000132
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.58e-7
Gnomad4 OTH exome
AF:
0.000130
GnomAD4 genome
AF:
0.000487
AC:
74
AN:
152094
Hom.:
0
Cov.:
33
AF XY:
0.000430
AC XY:
32
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00166
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000947
Bravo
AF:
0.000502

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 17, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
CADD
Benign
6.9
DANN
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs574986145; hg19: chr16-88772974; API