rs2910202

chr5-160423692-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004219.4(PTTG1):c.277-545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,168 control chromosomes in the GnomAD database, including 4,672 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 0.23 (4672 hom., cov: 32)
• Consequence: PTTG1 NM_004219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTTG1	NM_004219.4	c.277-545C>T		intron_variant		ENST00000352433.10
PTTG1	NM_001282382.1	c.277-545C>T		intron_variant
PTTG1	NM_001282383.1	c.277-545C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTTG1	ENST00000352433.10	c.277-545C>T		intron_variant		1	NM_004219.4	P1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35552 AN: 152048 Hom.: 4667 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35583 AN: 152168 Hom.: 4672 Cov.: 32 AF XY: 0.235 AC XY: 17457 AN XY: 74394

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.221

Alfa AF: 0.262 Hom.: 891

Bravo AF: 0.232

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.5
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs2910202; hg19: chr5-159850699;