NM_016166.3:c.78C>T

Variant names:

• chr15-68086359-C-T
• rs34515007
• NM_016166.3:c.78C>T

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.78C>T​(p.Ala26Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000611 in 1,612,882 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 0.0029 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (5 hom.)
• Consequence: PIAS1 NM_016166.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.470
• Publications: 3 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=-0.57).
• BP6: Variant 15-68086359-C-T is Benign according to our data. Variant chr15-68086359-C-T is described in ClinVar as Benign. ClinVar VariationId is 716410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.47 with no splicing effect.
• BS2: High AC in GnomAd4 at 445 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.78C>T	p.Ala26Ala	synonymous	Exon 2 of 14	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.84C>T	p.Ala28Ala	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.78C>T	p.Ala26Ala	synonymous	Exon 2 of 14	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.78C>T	p.Ala26Ala	synonymous	Exon 2 of 15	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.180C>T	p.Ala60Ala	synonymous	Exon 3 of 15	ENSP00000569796.1

Frequencies

GnomAD3 genomes AF: 0.00293 AC: 446 AN: 152008 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.0000588

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000893 AC: 220 AN: 246472 AF XY: 0.000725

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.000731

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000567

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000108

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.000370 AC: 541 AN: 1460756 Hom.: 5 Cov.: 31 AF XY: 0.000329 AC XY: 239 AN XY: 726600

African (AFR) AF: 0.0119 AC: 399 AN: 33462

American (AMR) AF: 0.000696 AC: 31 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111400

Other (OTH) AF: 0.000729 AC: 44 AN: 60350

GnomAD4 genome AF: 0.00293 AC: 445 AN: 152126 Hom.: 4 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74364

African (AFR) AF: 0.0104 AC: 431 AN: 41526

American (AMR) AF: 0.000393 AC: 6 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67984

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.00335

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-0.57
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs34515007; hg19: chr15-68378697; COSMIC: COSV51033466;