Variant 20-31771626-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012112.5(TPX2):c.552A>G(p.Ala184Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,613,932 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 113 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 99 hom. )

Consequence

TPX2
NM_012112.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.676

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 20-31771626-A-G is Benign according to our data. Variant chr20-31771626-A-G is described in ClinVar as [Benign]. Clinvar id is 775646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.676 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPX2	NM_012112.5 linkuse as main transcript	c.552A>G	p.Ala184Ala	synonymous_variant	7/18	ENST00000300403.11	NP_036244.2	Q9ULW0-1Q643R0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPX2	ENST00000300403.11 linkuse as main transcript	c.552A>G	p.Ala184Ala	synonymous_variant	7/18	1	NM_012112.5	ENSP00000300403.6		Q9ULW0-1
TPX2	ENST00000340513.4 linkuse as main transcript	c.552A>G	p.Ala184Ala	synonymous_variant	7/19	1		ENSP00000341145.4		Q9ULW0-2

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3151

AN:

152152

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0711

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00556

AC:

1396

AN:

251258

Hom.:

AF XY:

0.00415

AC XY:

563

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0692

Gnomad AMR exome

AF:

0.00469

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000686

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00237

AC:

3462

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1503

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.0729

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000336

Gnomad4 OTH exome

AF:

0.00613

GnomAD4 genome

AF:

0.0207

AC:

3156

AN:

152270

Hom.:

113

Cov.:

AF XY:

0.0198

AC XY:

1471

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0711

Gnomad4 AMR

AF:

0.00778

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0238

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.2

DANN

Benign

0.35

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.

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