15-68153576-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_016166.3(PIAS1):c.829-5dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,162,076 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (8 hom.)
• Consequence: PIAS1 NM_016166.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

Genes affected

PIAS1 (HGNC:2752): (protein inhibitor of activated STAT 1) This gene encodes a member of the protein inhibitor of activated STAT (PIAS) family. PIAS proteins function as SUMO E3 ligases and play important roles in many cellular processes by mediating the sumoylation of target proteins. This protein plays a central role as a transcriptional coregulator of numerous cellular pathways includign the STAT1 and nuclear factor kappaB pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-68153576-C-CT is Benign according to our data. Variant chr15-68153576-C-CT is described in ClinVar as [Benign]. Clinvar id is 1643727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00129 (196/151730) while in subpopulation EAS AF= 0.0282 (145/5146). AF 95% confidence interval is 0.0244. There are 3 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 197 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIAS1	NM_016166.3	c.829-5dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000249636.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIAS1	ENST00000249636.11	c.829-5dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016166.3	P1
PIAS1	ENST00000545237.1	c.835-5dup		splice_polypyrimidine_tract_variant, intron_variant		2
PIAS1	ENST00000564009.1	n.40-5dup		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 197 AN: 151620 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000678

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000526

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000959

GnomAD4 exome AF: 0.00289 AC: 2915 AN: 1010346 Hom.: 8 Cov.: 15 AF XY: 0.00279 AC XY: 1445 AN XY: 517428

Gnomad4 AFR exome AF: 0.00218

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00135

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.00168

Gnomad4 FIN exome AF: 0.000565

Gnomad4 NFE exome AF: 0.00231

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.00129 AC: 196 AN: 151730 Hom.: 3 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74148

Gnomad4 AFR AF: 0.000677

Gnomad4 AMR AF: 0.000525

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0282

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00142

Asia WGS AF: 0.0130 AC: 46 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2023

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Computational scores

Source: dbNSFP v4.3

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: rs201112127; hg19: chr15-68445914;