Variant 5-665261-C-T 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_007030.3(TPPP):c.501G>A(p.Thr167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,612 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 31 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 126 hom. )

Consequence

TPPP
NM_007030.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.96

Variant links:

Genes affected

TPPP (HGNC:24164): (tubulin polymerization promoting protein) Enables several functions, including GTPase activity; magnesium ion binding activity; and protein homodimerization activity. Involved in several processes, including microtubule cytoskeleton organization; negative regulation of tubulin deacetylation; and positive regulation of protein polymerization. Located in several cellular components, including mitochondrion; mitotic spindle; and perinuclear region of cytoplasm. Colocalizes with microtubule and microtubule bundle. [provided by Alliance of Genome Resources, Apr 2022]

TPPP links:

CEP72 (HGNC:25547): (centrosomal protein 72) The product of this gene is a member of the leucine-rich-repeat (LRR) superfamily of proteins. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. [provided by RefSeq, Jul 2008]

CEP72 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 5-665261-C-T is Benign according to our data. Variant chr5-665261-C-T is described in ClinVar as [Benign]. Clinvar id is 771367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.96 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPPP	NM_007030.3 linkuse as main transcript	c.501G>A	p.Thr167=	synonymous_variant	4/4	ENST00000360578.7	NP_008961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPPP	ENST00000360578.7 linkuse as main transcript	c.501G>A	p.Thr167=	synonymous_variant	4/4	1	NM_007030.3	ENSP00000353785	P1
CEP72	ENST00000514507.1 linkuse as main transcript	n.369C>T		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00591

AC:

899

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0509

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0120

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.0112

AC:

2793

AN:

250066

Hom.:

AF XY:

0.00873

AC XY:

1182

AN XY:

135408

show subpopulations

Gnomad AFR exome

AF:

0.000495

Gnomad AMR exome

AF:

0.0743

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00735

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00772

GnomAD4 exome

AF:

0.00287

AC:

4196

AN:

1461452

Hom.:

126

Cov.:

AF XY:

0.00251

AC XY:

1827

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.0686

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0195

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.00291

GnomAD4 genome

AF:

0.00599

AC:

911

AN:

152160

Hom.:

Cov.:

AF XY:

0.00672

AC XY:

500

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.0512

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00920

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.9

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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