5-160423365-C-T

Position:

• chr5-160423365-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.276+472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,058 control chromosomes in the GnomAD database, including 25,970 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 0.56 (25970 hom., cov: 33)
• Consequence: PTTG1 NM_004219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTTG1	NM_004219.4	c.276+472C>T		intron_variant		ENST00000352433.10	NP_004210.1
PTTG1	NM_001282382.1	c.276+472C>T		intron_variant			NP_001269311.1
PTTG1	NM_001282383.1	c.276+472C>T		intron_variant			NP_001269312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTTG1	ENST00000352433.10	c.276+472C>T		intron_variant		1	NM_004219.4	ENSP00000344936.5

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85564 AN: 151938 Hom.: 25958 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.563 AC: 85605 AN: 152058 Hom.: 25970 Cov.: 33 AF XY: 0.565 AC XY: 42022 AN XY: 74316

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.572

Alfa AF: 0.642 Hom.: 29724

Bravo AF: 0.548

Asia WGS AF: 0.431 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.67

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: rs2910201; hg19: chr5-159850372;