14-21032055-C-T

Variant summary

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

The NM_173846.5(TPPP2):​c.491C>T​(p.Thr164Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TPPP2
NM_173846.5 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98
Variant links:
Genes affected
TPPP2 (HGNC:19293): (tubulin polymerization promoting protein family member 2) Enables tubulin binding activity. Involved in regulation of flagellated sperm motility. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

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
TPPP2NM_173846.5 linkc.491C>T p.Thr164Ile missense_variant Exon 4 of 4 ENST00000321760.11 NP_776245.2 P59282

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPPP2ENST00000321760.11 linkc.491C>T p.Thr164Ile missense_variant Exon 4 of 4 1 NM_173846.5 ENSP00000317595.6 P59282

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251174
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000994
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:
0.00000137
AC:
2
AN:
1461610
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727050
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.491C>T (p.T164I) alteration is located in exon 4 (coding exon 3) of the TPPP2 gene. This alteration results from a C to T substitution at nucleotide position 491, causing the threonine (T) at amino acid position 164 to be replaced by an isoleucine (I). 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
Uncertain
0.52
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
T;T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
.;D
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Benign
-0.39
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.99
D;D
Vest4
0.67
MutPred
0.56
Loss of phosphorylation at T164 (P = 0.0041);Loss of phosphorylation at T164 (P = 0.0041);
MVP
0.22
MPC
0.37
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.76
gMVP
0.50

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: rs1458310383; hg19: chr14-21500214; API