rs6089071

chr20-31790581-C-Gchr20-31790581-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012112.5(TPX2):c.1414-2154C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,132 control chromosomes in the GnomAD database, including 7,484 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7484 hom., cov: 32)
• Consequence: TPX2 NM_012112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPX2	NM_012112.5	c.1414-2154C>G		intron_variant		ENST00000300403.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPX2	ENST00000300403.11	c.1414-2154C>G		intron_variant		1	NM_012112.5	P1
TPX2	ENST00000340513.4	c.1522-2154C>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43051 AN: 152014 Hom.: 7481 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0641

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.283 AC: 43083 AN: 152132 Hom.: 7484 Cov.: 32 AF XY: 0.281 AC XY: 20888 AN XY: 74376

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0640

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.253

Alfa AF: 0.151 Hom.: 298

Bravo AF: 0.288

Asia WGS AF: 0.0600 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	14
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs6089071; hg19: chr20-30378384;