13-19782801-T-A

Variant names:

• chr13-19782801-T-A
• rs9508887
• ENST00000471658.5:n.-44A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471658.5(PSPC1):​n.-44A>T variant causes a non coding transcript exon 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 ENST00000471658.5 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.0001372
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 21 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSPC1	NM_001354909.2	c.-44A>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000338910.9	NP_001341838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSPC1	ENST00000338910.9	c.-44A>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_001354909.2	ENSP00000343966.4

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

GnomAD2 exomes AF: 0.773 AC: 103971 AN: 134522 AF XY: 0.775

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 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

African (AFR) AF: 0.375 AC: 9918 AN: 26444

American (AMR) AF: 0.780 AC: 18551 AN: 23774

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 12564 AN: 19670

East Asian (EAS) AF: 0.913 AC: 31354 AN: 34336

South Asian (SAS) AF: 0.785 AC: 54057 AN: 68820

European-Finnish (FIN) AF: 0.877 AC: 31193 AN: 35582

Middle Eastern (MID) AF: 0.640 AC: 3145 AN: 4916

European-Non Finnish (NFE) AF: 0.791 AC: 846467 AN: 1069774

Other (OTH) AF: 0.757 AC: 41943 AN: 55388

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

African (AFR) AF: 0.395 AC: 16409 AN: 41520

American (AMR) AF: 0.751 AC: 11476 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2248 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4605 AN: 5184

South Asian (SAS) AF: 0.783 AC: 3786 AN: 4834

European-Finnish (FIN) AF: 0.875 AC: 9271 AN: 10600

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53841 AN: 68008

Other (OTH) AF: 0.678 AC: 1430 AN: 2110

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
PhyloP100		-0.45
PromoterAI		0.030	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9508887; hg19: chr13-20356941;