rs9551988

Variant names:

• chr13-19719577-C-T
• rs9551988
• NM_001354909.2:c.1159-9978G>A

Variant summary

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

The NM_001354909.2(PSPC1):​c.1159-9978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,192 control chromosomes in the GnomAD database, including 1,218 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 0.12 (1218 hom., cov: 32)
• Consequence: PSPC1 NM_001354909.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSPC1	NM_001354909.2	c.1159-9978G>A		intron_variant	Intron 6 of 8	ENST00000338910.9	NP_001341838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSPC1	ENST00000338910.9	c.1159-9978G>A		intron_variant	Intron 6 of 8	1	NM_001354909.2	ENSP00000343966.4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18190 AN: 152074 Hom.: 1219 Cov.: 32

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.120 AC: 18188 AN: 152192 Hom.: 1218 Cov.: 32 AF XY: 0.116 AC XY: 8665 AN XY: 74404

Gnomad4 AFR AF: 0.0956

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.0823

Gnomad4 FIN AF: 0.0775

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.150

Alfa AF: 0.129 Hom.: 221

Bravo AF: 0.127

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.77

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: rs9551988; hg19: chr13-20293717;