16-1350998-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001001410.3(TSR3):​c.335A>C​(p.Gln112Pro) variant causes a missense, splice region 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. 14/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TSR3
NM_001001410.3 missense, splice_region

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72
Variant links:
Genes affected
TSR3 (HGNC:14175): (TSR3 ribosome maturation factor) Enables transferase activity. Involved in enzyme-directed rRNA pseudouridine synthesis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2757754).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSR3NM_001001410.3 linkc.335A>C p.Gln112Pro missense_variant, splice_region_variant 3/6 ENST00000007390.3 NP_001001410.1 Q9UJK0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSR3ENST00000007390.3 linkc.335A>C p.Gln112Pro missense_variant, splice_region_variant 3/61 NM_001001410.3 ENSP00000007390.2 Q9UJK0
TSR3ENST00000566296.1 linkn.96A>C splice_region_variant, non_coding_transcript_exon_variant 2/43 ENSP00000455722.1 H3BQD4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 GeneticsApr 19, 2023The c.335A>C (p.Q112P) alteration is located in exon 3 (coding exon 3) of the TSR3 gene. This alteration results from a A to C substitution at nucleotide position 335, causing the glutamine (Q) at amino acid position 112 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
0.083
BayesDel_addAF
Benign
0.00010
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.49
N
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.15
Sift
Benign
0.086
T
Sift4G
Benign
0.13
T
Polyphen
0.0060
B
Vest4
0.54
MutPred
0.49
Loss of helix (P = 0.079);
MVP
0.15
MPC
0.069
ClinPred
0.28
T
GERP RS
4.1
Varity_R
0.50
gMVP
0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200577377; hg19: chr16-1400999; API