rs6089071

Variant names:

• chr20-31790581-C-G
• rs6089071
• NM_012112.5:c.1414-2154C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-31790581-C-G
• chr20-31790581-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

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.1414-2154C>G		intron	N/A	NP_036244.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPX2	ENST00000300403.11	TSL:1 MANE Select	c.1414-2154C>G		intron	N/A	ENSP00000300403.6	Q9ULW0-1
	TPX2	ENST00000340513.4	TSL:1	c.1522-2154C>G		intron	N/A	ENSP00000341145.4	Q9ULW0-2
	TPX2	ENST00000934062.1		c.1522-2154C>G		intron	N/A	ENSP00000604121.1

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

African (AFR) AF: 0.478 AC: 19802 AN: 41460

American (AMR) AF: 0.205 AC: 3142 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3464

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0640 AC: 309 AN: 4830

European-Finnish (FIN) AF: 0.321 AC: 3397 AN: 10598

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14899 AN: 67990

Other (OTH) AF: 0.253 AC: 534 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6089071; hg19: chr20-30378384;