ENST00000471658.5:n.-44A>C

Variant names:

• chr13-19782961-A-G
• ENST00000619300.4:c.-79T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000471658.5(PSPC1):​n.-204T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSPC1 ENST00000471658.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSPC1	NM_001354909.2	c.-204T>C		upstream_gene_variant		ENST00000338910.9	NP_001341838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSPC1	ENST00000338910.9	c.-204T>C		upstream_gene_variant		1	NM_001354909.2	ENSP00000343966.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 341150 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 172662

African (AFR) AF: 0.00 AC: 0 AN: 8398

American (AMR) AF: 0.00 AC: 0 AN: 7604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9858

East Asian (EAS) AF: 0.00 AC: 0 AN: 23246

South Asian (SAS) AF: 0.00 AC: 0 AN: 10774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1480

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 237502

Other (OTH) AF: 0.00 AC: 0 AN: 19966

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.40
PromoterAI		0.072	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr13-20357101;