rs1895320

Positions:

• chr5-160422579-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTTG1	NM_004219.4	c.92-130A>G		intron_variant		ENST00000352433.10	NP_004210.1
PTTG1	NM_001282382.1	c.92-130A>G		intron_variant			NP_001269311.1
PTTG1	NM_001282383.1	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	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.: 32

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

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.: 13 AF XY: 0.150 AC XY: 74269 AN XY: 495624

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.: 32 AF XY: 0.140 AC XY: 10404 AN XY: 74366

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

Other links and lift over

dbSNP: rs1895320; hg19: chr5-159849586;