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GeneBe

9-86301591-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_024617.4(TUT7):c.4105C>T(p.Arg1369Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,904 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1369Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TUT7
NM_024617.4 missense

Scores

2
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47
Variant links:
Genes affected
TUT7 (HGNC:25817): (terminal uridylyl transferase 7) Enables RNA uridylyltransferase activity and miRNA binding activity. Involved in RNA metabolic process and negative regulation of transposition, RNA-mediated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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;
PP2
Missense variant where missense usually causes diseases, TUT7
BP4
Computational evidence support a benign effect (MetaRNN=0.37365776).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TUT7NM_024617.4 linkuse as main transcriptc.4105C>T p.Arg1369Trp missense_variant 26/27 ENST00000375963.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TUT7ENST00000375963.8 linkuse as main transcriptc.4105C>T p.Arg1369Trp missense_variant 26/275 NM_024617.4 P1Q5VYS8-1
TUT7ENST00000375960.6 linkuse as main transcriptc.3397C>T p.Arg1133Trp missense_variant 19/201 Q5VYS8-4
TUT7ENST00000277141.10 linkuse as main transcriptc.1972C>T p.Arg658Trp missense_variant 27/282
TUT7ENST00000375957.5 linkuse as main transcriptc.805C>T p.Arg269Trp missense_variant 11/122

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250382
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135404
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460904
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726836
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:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 26, 2022The c.4105C>T (p.R1369W) alteration is located in exon 26 (coding exon 25) of the ZCCHC6 gene. This alteration results from a C to T substitution at nucleotide position 4105, causing the arginine (R) at amino acid position 1369 to be replaced by a tryptophan (W). 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
0.26
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.24
Cadd
Uncertain
24
Dann
Uncertain
1.0
Eigen
Benign
0.11
Eigen_PC
Benign
0.076
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.37
T;T;T;T
MetaSVM
Benign
-0.49
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-4.1
D;D;D;D
REVEL
Benign
0.21
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;D;.;D
Vest4
0.42
MutPred
0.38
.;.;.;Loss of helix (P = 0.0033);
MVP
0.28
MPC
1.7
ClinPred
0.99
D
GERP RS
3.9
Varity_R
0.36
gMVP
0.40

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: rs754403647; hg19: chr9-88916506; API