rs775705725

Variant names:

• chr15-68086356-C-T
• rs775705725
• NM_016166.3:c.75C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_016166.3(PIAS1):​c.75C>T​(p.Tyr25Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PIAS1 NM_016166.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 15-68086356-C-T is Benign according to our data. Variant chr15-68086356-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3621716.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.11 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016166.3. 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
	PIAS1	NM_016166.3	MANE Select	c.75C>T	p.Tyr25Tyr	synonymous	Exon 2 of 14	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.81C>T	p.Tyr27Tyr	synonymous	Exon 3 of 15	NP_001307616.1	O75925-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIAS1	ENST00000249636.11	TSL:1 MANE Select	c.75C>T	p.Tyr25Tyr	synonymous	Exon 2 of 14	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.75C>T	p.Tyr25Tyr	synonymous	Exon 2 of 15	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.177C>T	p.Tyr59Tyr	synonymous	Exon 3 of 15	ENSP00000569796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 245972 AF XY: 0.0000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000586

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1460544 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 726468

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000674 AC: 3 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111304

Other (OTH) AF: 0.0000166 AC: 1 AN: 60336

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.54
PhyloP100		2.1
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

Other links and lift over

dbSNP: rs775705725; hg19: chr15-68378694; COSMIC: COSV107220330;