15-68086677-C-G

Variant names:

• chr15-68086677-C-G
• rs182474538
• NM_016166.3:c.396C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016166.3(PIAS1):​c.396C>G​(p.Val132Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 1,613,318 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (3 hom.)
• Consequence: PIAS1 NM_016166.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.227
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-68086677-C-G is Benign according to our data. Variant chr15-68086677-C-G is described in ClinVar as Benign. ClinVar VariationId is 782599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.227 with no splicing effect.
• BS2: High AC in GnomAd4 at 409 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.396C>G	p.Val132Val	synonymous	Exon 2 of 14	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.402C>G	p.Val134Val	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.396C>G	p.Val132Val	synonymous	Exon 2 of 14	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.396C>G	p.Val132Val	synonymous	Exon 2 of 15	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.498C>G	p.Val166Val	synonymous	Exon 3 of 15	ENSP00000569796.1

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 408 AN: 152132 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00944

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000631 AC: 157 AN: 248958 AF XY: 0.000422

Gnomad AFR exome AF: 0.00930

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000281 AC: 411 AN: 1461068 Hom.: 3 Cov.: 30 AF XY: 0.000239 AC XY: 174 AN XY: 726876

African (AFR) AF: 0.00983 AC: 329 AN: 33460

American (AMR) AF: 0.000313 AC: 14 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111294

Other (OTH) AF: 0.000862 AC: 52 AN: 60356

GnomAD4 genome AF: 0.00269 AC: 409 AN: 152250 Hom.: 1 Cov.: 32 AF XY: 0.00254 AC XY: 189 AN XY: 74446

African (AFR) AF: 0.00944 AC: 392 AN: 41542

American (AMR) AF: 0.000720 AC: 11 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.000915 Hom.: 0

Bravo AF: 0.00327

ClinVar

ClinVar submissions

Significance: 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	-0.47
CADD	Benign	7.0
DANN	Benign	0.70
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs182474538; hg19: chr15-68379015;