Variant 5-677743-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_007030.3(TPPP):c.311+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,548,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TPPP
NM_007030.3 splice_region, intron

Scores

Splicing: ADA: 0.0002085

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 5-677743-C-A is Benign according to our data. Variant chr5-677743-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 751578.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
TPPP	NM_007030.3 linkuse as main transcript	c.311+7G>T	splice_region_variant, intron_variant	ENST00000360578.7	NP_008961.1
TPPP	XM_017008993.2 linkuse as main transcript	c.512+7G>T	splice_region_variant, intron_variant		XP_016864482.1
TPPP	XM_024454346.1 linkuse as main transcript	c.311+7G>T	splice_region_variant, intron_variant		XP_024310114.1
TPPP	XM_047416674.1 linkuse as main transcript	c.311+7G>T	splice_region_variant, intron_variant		XP_047272630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPPP	ENST00000360578.7 linkuse as main transcript	c.311+7G>T		splice_region_variant, intron_variant		1	NM_007030.3	ENSP00000353785	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000975

AC:

AN:

205172

Hom.:

AF XY:

0.00000913

AC XY:

AN XY:

109476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1395740

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

686218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.0000520

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.6

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.0

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