Variant 16-67390343-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015964.4(TPPP3):c.362C>T(p.Ala121Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,824 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TPPP3
NM_015964.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

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]

TPPP3 links:

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/exons	MANE	Protein
TPPP3	NM_015964.4 linkuse as main transcript	c.362C>T	p.Ala121Val	missense_variant	4/4	ENST00000393957.7	NP_057048.2
TPPP3	NM_016140.4 linkuse as main transcript	c.362C>T	p.Ala121Val	missense_variant	5/5		NP_057224.2
TPPP3	XM_024450294.2 linkuse as main transcript	c.362C>T	p.Ala121Val	missense_variant	4/4		XP_024306062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TPPP3	ENST00000393957.7 linkuse as main transcript	c.362C>T	p.Ala121Val	missense_variant	4/4	1	NM_015964.4	ENSP00000377529	P1
TPPP3	ENST00000564104.5 linkuse as main transcript	c.362C>T	p.Ala121Val	missense_variant	3/3	1		ENSP00000462435	P1
TPPP3	ENST00000290942.9 linkuse as main transcript	c.362C>T	p.Ala121Val	missense_variant	5/5	2		ENSP00000290942	P1
TPPP3	ENST00000562206.1 linkuse as main transcript	c.362C>T	p.Ala121Val	missense_variant	4/4	2		ENSP00000457275	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727106

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

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

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 submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.362C>T (p.A121V) alteration is located in exon 5 (coding exon 3) of the TPPP3 gene. This alteration results from a C to T substitution at nucleotide position 362, causing the alanine (A) at amino acid position 121 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.054

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

.;.;.;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

N;.;N;N

REVEL

Benign

0.074

Sift

Benign

0.20

T;.;T;T

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.027

B;B;B;B

Vest4

0.39

MutPred

0.49

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.56

MPC

0.62

ClinPred

0.92

GERP RS

3.9

Varity_R

0.19

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -6

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over