Variant chr5-160422579-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004219.4(PTTG1):c.92-130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,115,174 control chromosomes in the GnomAD database, including 12,524 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 0.14 ( 1547 hom., cov: 32)

Exomes 𝑓: 0.15 ( 10977 hom. )

Consequence

PTTG1
NM_004219.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

PTTG1 (HGNC:9690): (PTTG1 regulator of sister chromatid separation, securin) The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. It is an anaphase-promoting complex (APC) substrate that associates with a separin until activation of the APC. The gene product has transforming activity in vitro and tumorigenic activity in vivo, and the gene is highly expressed in various tumors. The gene product contains 2 PXXP motifs, which are required for its transforming and tumorigenic activities, as well as for its stimulation of basic fibroblast growth factor expression. It also contains a destruction box (D box) that is required for its degradation by the APC. The acidic C-terminal region of the encoded protein can act as a transactivation domain. The gene product is mainly a cytosolic protein, although it partially localizes in the nucleus. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

PTTG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PTTG1	NM_004219.4 linkuse as main transcript	c.92-130A>G	intron_variant	ENST00000352433.10	NP_004210.1
PTTG1	NM_001282382.1 linkuse as main transcript	c.92-130A>G	intron_variant		NP_001269311.1
PTTG1	NM_001282383.1 linkuse as main transcript	c.92-130A>G	intron_variant		NP_001269312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTTG1	ENST00000352433.10 linkuse as main transcript	c.92-130A>G		intron_variant		1	NM_004219.4	ENSP00000344936	P1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21289

AN:

151998

Hom.:

1547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.0988

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.151

AC:

28819

AN:

190454

Hom.:

2390

AF XY:

0.157

AC XY:

16168

AN XY:

103044

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0755

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.214

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.147

AC:

141465

AN:

963058

Hom.:

10977

Cov.:

AF XY:

0.150

AC XY:

74269

AN XY:

495624

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0807

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.140

AC:

21297

AN:

152116

Hom.:

1547

Cov.:

AF XY:

0.140

AC XY:

10404

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0987

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.148

Hom.:

2061

Bravo

AF:

0.135

Asia WGS

AF:

0.200

AC:

699

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.3

DANN

Benign

0.40

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over