rs9508887

chr13-19782801-T-Achr13-19782801-T-Cchr13-19782801-T-G

Variant summary

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

The NM_001354909.2(PSPC1):c.-44A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,490,910 control chromosomes in the GnomAD database, including 453,029 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 0.68 (38203 hom., cov: 34)
  • Exomes 𝑓: 0.78 (414826 hom.)
• Consequence: PSPC1 NM_001354909.2 5_prime_UTR
• Scores: Splicing: ADA: 0.0001372
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

Genes affected

PSPC1 (HGNC:20320): (paraspeckle component 1) This gene encodes a nucleolar protein that localizes to punctate subnuclear structures that occur close to splicing speckles, known as paraspeckles. These paraspeckles are composed of RNA-protein structures that include a non-coding RNA, NEAT1/Men epsilon/beta, and the Drosophila Behavior Human Splicing family of proteins, which include the product of this gene and the P54NRB/NONO and PSF/SFPQ proteins. Paraspeckles may function in the control of gene expression via an RNA nuclear retention mechanism. The protein encoded by this gene is found in paraspeckles in transcriptionally active cells, but it localizes to unique cap structures at the nucleolar periphery when RNA polymerase II transcription is inhibited, or during telophase. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene, which is also located on chromosome 13, has been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSPC1	NM_001354909.2	c.-44A>T		5_prime_UTR_variant	1/9	ENST00000338910.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSPC1	ENST00000338910.9	c.-44A>T		5_prime_UTR_variant	1/9	1	NM_001354909.2	P1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 104031 AN: 152088 Hom.: 38210 Cov.: 34

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.682

GnomAD3 exomes AF: 0.773 AC: 103971 AN: 134522 Hom.: 41121 AF XY: 0.775 AC XY: 58391 AN XY: 75306

Gnomad AFR exome AF: 0.388

Gnomad AMR exome AF: 0.789

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.899

Gnomad SAS exome AF: 0.788

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.787

Gnomad OTH exome AF: 0.765

GnomAD4 exome AF: 0.784 AC: 1049192 AN: 1338704 Hom.: 414826 Cov.: 35 AF XY: 0.784 AC XY: 519718 AN XY: 662924

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.913

Gnomad4 SAS exome AF: 0.785

Gnomad4 FIN exome AF: 0.877

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.757

GnomAD4 genome AF: 0.684 AC: 104047 AN: 152206 Hom.: 38203 Cov.: 34 AF XY: 0.689 AC XY: 51270 AN XY: 74438

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.678

Alfa AF: 0.683 Hom.: 2671

Bravo AF: 0.660

Asia WGS AF: 0.764 AC: 2655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	7.2
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0020
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: rs9508887; hg19: chr13-20356941;