NM_022830.3:c.1928G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022830.3(TUT1):​c.1928G>C​(p.Arg643Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R643Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TUT1
NM_022830.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
Variant links:
Genes affected
TUT1 (HGNC:26184): (terminal uridylyl transferase 1, U6 snRNA-specific) This gene encodes a nucleotidyl transferase that functions as both a terminal uridylyltransferase and a nuclear poly(A) polymerase. The encoded enzyme specifically adds and removes nucleotides from the 3' end of small nuclear RNAs and select mRNAs and may function in controlling gene expression and cell proliferation.[provided by RefSeq, Apr 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUT1NM_022830.3 linkc.1928G>C p.Arg643Pro missense_variant Exon 9 of 9 ENST00000476907.6 NP_073741.3 Q9H6E5A0A0A8K9B1F5H0R1
TUT1NM_001367906.1 linkc.*342G>C 3_prime_UTR_variant Exon 9 of 9 NP_001354835.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUT1ENST00000476907.6 linkc.1928G>C p.Arg643Pro missense_variant Exon 9 of 9 1 NM_022830.3 ENSP00000419607.1 Q9H6E5
ENSG00000255508ENST00000496634.2 linkn.1474+866G>C intron_variant Intron 8 of 16 2 ENSP00000456163.1 H3BRB1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2042G>C (p.R681P) alteration is located in exon 9 (coding exon 9) of the TUT1 gene. This alteration results from a G to C substitution at nucleotide position 2042, causing the arginine (R) at amino acid position 681 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.040
.;T
Eigen
Benign
-0.018
Eigen_PC
Benign
-0.058
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.93
N;N
REVEL
Benign
0.14
Sift
Benign
0.13
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.95
P;P
Vest4
0.50
MutPred
0.25
Gain of glycosylation at R681 (P = 0.0233);.;
MVP
0.53
MPC
0.92
ClinPred
0.71
D
GERP RS
5.0
Varity_R
0.22
gMVP
0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62343263; API