13-19718460-A-G

Variant names:

• chr13-19718460-A-G
• rs3858741
• NM_001354909.2:c.1159-8861T>C

Variant summary

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

The NM_001354909.2(PSPC1):​c.1159-8861T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 152,360 control chromosomes in the GnomAD database, including 62 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 0.017 (62 hom., cov: 31)
• Consequence: PSPC1 NM_001354909.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354909.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSPC1	NM_001354909.2	MANE Select	c.1159-8861T>C		intron	N/A	NP_001341838.1	Q8WXF1-1
	PSPC1	NM_001042414.4		c.1159-8861T>C		intron	N/A	NP_001035879.1	Q8WXF1-1
	PSPC1	NM_001354908.2		c.1187+2993T>C		intron	N/A	NP_001341837.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSPC1	ENST00000338910.9	TSL:1 MANE Select	c.1159-8861T>C		intron	N/A	ENSP00000343966.4	Q8WXF1-1
	PSPC1	ENST00000471658.5	TSL:1	n.1158+11779T>C		intron	N/A	ENSP00000436038.1	Q8WXF1-2
	PSPC1	ENST00000946081.1		c.1468-8861T>C		intron	N/A	ENSP00000616140.1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2646 AN: 152242 Hom.: 62 Cov.: 31

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0124

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

GnomAD4 genome AF: 0.0174 AC: 2647 AN: 152360 Hom.: 62 Cov.: 31 AF XY: 0.0172 AC XY: 1280 AN XY: 74516

African (AFR) AF: 0.0583 AC: 2424 AN: 41580

American (AMR) AF: 0.0108 AC: 165 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68036

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.00286 Hom.: 18

Bravo AF: 0.0199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.24
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3858741; hg19: chr13-20292600;