Genetic Variant NM_012112.5:c.976C>T (chr20-31778906-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012112.5(TPX2):c.976C>T(p.Pro326Ser) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TPX2
NM_012112.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.743

Publications

0 publications found

Variant links:

Genes affected

TPX2 (HGNC:1249): (TPX2 microtubule nucleation factor) Enables importin-alpha family protein binding activity and protein kinase binding activity. Involved in activation of protein kinase activity; microtubule cytoskeleton organization; and negative regulation of microtubule depolymerization. Located in intercellular bridge; mitotic spindle; and nucleoplasm. Colocalizes with spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

TPX2 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

TPX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11046699).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012112.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPX2	NM_012112.5	MANE Select	c.976C>T	p.Pro326Ser	missense	Exon 10 of 18	NP_036244.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPX2	ENST00000300403.11	TSL:1 MANE Select	c.976C>T	p.Pro326Ser	missense	Exon 10 of 18	ENSP00000300403.6	Q9ULW0-1
TPX2	ENST00000340513.4	TSL:1	c.976C>T	p.Pro326Ser	missense	Exon 10 of 19	ENSP00000341145.4	Q9ULW0-2
TPX2	ENST00000934062.1		c.976C>T	p.Pro326Ser	missense	Exon 10 of 19	ENSP00000604121.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459934

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726332

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

43994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

85832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111576

Other (OTH)

AF:

0.00

AC:

AN:

60304

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.020

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.82

M_CAP

Benign

0.0045

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

0.74

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.88

REVEL

Benign

0.065

Sift

Benign

0.72

Sift4G

Benign

0.44

Polyphen

0.048

Vest4

0.26

MutPred

0.46

Gain of helix (P = 0.0143)

MVP

0.16

MPC

0.12

ClinPred

0.29

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.28

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over