rs115949457

Variant names:

• chr20-31766608-C-T
• rs115949457
• NM_012112.5:c.282C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_012112.5(TPX2):​c.282C>T​(p.Ser94Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,613,472 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (20 hom., cov: 30)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: TPX2 NM_012112.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.74
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-31766608-C-T is Benign according to our data. Variant chr20-31766608-C-T is described in ClinVar as Benign. ClinVar VariationId is 785652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1677/151896) while in subpopulation AFR AF = 0.0387 (1601/41418). AF 95% confidence interval is 0.0371. There are 20 homozygotes in GnomAd4. There are 776 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 Unknown gene

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.282C>T	p.Ser94Ser	synonymous	Exon 5 of 18	NP_036244.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPX2	ENST00000300403.11	TSL:1 MANE Select	c.282C>T	p.Ser94Ser	synonymous	Exon 5 of 18	ENSP00000300403.6	Q9ULW0-1
	TPX2	ENST00000340513.4	TSL:1	c.282C>T	p.Ser94Ser	synonymous	Exon 5 of 19	ENSP00000341145.4	Q9ULW0-2
	TPX2	ENST00000934062.1		c.282C>T	p.Ser94Ser	synonymous	Exon 5 of 19	ENSP00000604121.1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1673 AN: 151778 Hom.: 20 Cov.: 30

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00349

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: 0.0000882

Gnomad OTH AF: 0.00817

GnomAD2 exomes AF: 0.00311 AC: 781 AN: 251126 AF XY: 0.00239

Gnomad AFR exome AF: 0.0446

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.00109 AC: 1592 AN: 1461576 Hom.: 31 Cov.: 33 AF XY: 0.000926 AC XY: 673 AN XY: 727078

African (AFR) AF: 0.0409 AC: 1368 AN: 33448

American (AMR) AF: 0.00161 AC: 72 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111874

Other (OTH) AF: 0.00214 AC: 129 AN: 60382

GnomAD4 genome AF: 0.0110 AC: 1677 AN: 151896 Hom.: 20 Cov.: 30 AF XY: 0.0105 AC XY: 776 AN XY: 74236

African (AFR) AF: 0.0387 AC: 1601 AN: 41418

American (AMR) AF: 0.00349 AC: 53 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67984

Other (OTH) AF: 0.00808 AC: 17 AN: 2104

Alfa AF: 0.00507 Hom.: 11

Bravo AF: 0.0127

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.65
DANN	Benign	0.43
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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: rs115949457; hg19: chr20-30354411;