15-68086599-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_016166.3(PIAS1):c.318G>A(p.Ser106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,613,770 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (6 hom.)
• Consequence: PIAS1 NM_016166.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-68086599-G-A is Benign according to our data. Variant chr15-68086599-G-A is described in ClinVar as [Benign]. Clinvar id is 1563059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000874 (133/152130) while in subpopulation EAS AF= 0.0218 (113/5178). AF 95% confidence interval is 0.0186. There are 3 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIAS1	NM_016166.3	c.318G>A	p.Ser106=	synonymous_variant	2/14	ENST00000249636.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIAS1	ENST00000249636.11	c.318G>A	p.Ser106=	synonymous_variant	2/14	1	NM_016166.3	P1
PIAS1	ENST00000545237.1	c.324G>A	p.Ser108=	synonymous_variant	3/15	2
PIAS1	ENST00000564915.5	c.318G>A	p.Ser106=	synonymous_variant, NMD_transcript_variant	2/5	5
PIAS1	ENST00000562190.1	c.*408G>A		3_prime_UTR_variant, NMD_transcript_variant	4/6	3

Frequencies

GnomAD3 genomes AF: 0.000875 AC: 133 AN: 152012 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00155 AC: 386 AN: 249144 Hom.: 2 AF XY: 0.00138 AC XY: 186 AN XY: 135154

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0210

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000473 AC: 692 AN: 1461640 Hom.: 6 Cov.: 31 AF XY: 0.000448 AC XY: 326 AN XY: 727110

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0139

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.000874 AC: 133 AN: 152130 Hom.: 3 Cov.: 32 AF XY: 0.000807 AC XY: 60 AN XY: 74334

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000535 Hom.: 0

Bravo AF: 0.00103

Asia WGS AF: 0.00549 AC: 19 AN: 3478

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 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	9.5
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs145053928; hg19: chr15-68378937; COSMIC: COSV99987134;