16-67390484-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015964.4(TPPP3):​c.337G>A​(p.Val113Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,613,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

TPPP3
NM_015964.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82
Variant links:
Genes affected
TPPP3 (HGNC:24162): (tubulin polymerization promoting protein family member 3) Enables tubulin binding activity. Involved in decidualization and microtubule bundle formation. Colocalizes with microtubule bundle and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
RNU1-123P (HGNC:48465): (RNA, U1 small nuclear 123, pseudogene)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11011621).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPPP3NM_015964.4 linkc.337G>A p.Val113Ile missense_variant Exon 3 of 4 ENST00000393957.7 NP_057048.2 Q9BW30A0A024R702
TPPP3NM_016140.4 linkc.337G>A p.Val113Ile missense_variant Exon 4 of 5 NP_057224.2 Q9BW30A0A024R702
TPPP3XM_024450294.2 linkc.337G>A p.Val113Ile missense_variant Exon 3 of 4 XP_024306062.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPPP3ENST00000393957.7 linkc.337G>A p.Val113Ile missense_variant Exon 3 of 4 1 NM_015964.4 ENSP00000377529.2 Q9BW30

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000459
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
250820
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135550
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000794
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1461486
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
727056
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152106
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.000459
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.000144
ESP6500AA
AF:
0.000682
AC:
3
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.337G>A (p.V113I) alteration is located in exon 4 (coding exon 2) of the TPPP3 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the valine (V) at amino acid position 113 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
Benign
0.070
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.037
T;T;T;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.81
.;.;.;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;L;L;L
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.68
N;.;N;N
REVEL
Benign
0.084
Sift
Benign
0.16
T;.;T;T
Sift4G
Benign
0.33
T;T;T;T
Polyphen
0.0010
B;B;B;B
Vest4
0.12
MVP
0.37
MPC
0.30
ClinPred
0.081
T
GERP RS
3.7
Varity_R
0.056
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs146906089; hg19: chr16-67424387; COSMIC: COSV52083743; COSMIC: COSV52083743; API