Menu
GeneBe

15-68086359-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016166.3(PIAS1):c.78C>T(p.Ala26=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.470
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-68086359-C-T is Benign according to our data. Variant chr15-68086359-C-T is described in ClinVar as [Benign]. Clinvar id is 716410.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.47 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 446 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIAS1NM_016166.3 linkuse as main transcriptc.78C>T p.Ala26= synonymous_variant 2/14 ENST00000249636.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIAS1ENST00000249636.11 linkuse as main transcriptc.78C>T p.Ala26= synonymous_variant 2/141 NM_016166.3 P1O75925-1
PIAS1ENST00000545237.1 linkuse as main transcriptc.84C>T p.Ala28= synonymous_variant 3/152 O75925-2
PIAS1ENST00000564915.5 linkuse as main transcriptc.78C>T p.Ala26= synonymous_variant, NMD_transcript_variant 2/55
PIAS1ENST00000562190.1 linkuse as main transcriptc.*168C>T 3_prime_UTR_variant, NMD_transcript_variant 4/63

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00293
AC:
446
AN:
152008
Hom.:
4
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.000893
AC:
220
AN:
246472
Hom.:
0
AF XY:
0.000725
AC XY:
97
AN XY:
133784
show subpopulations
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 SAS exome
AF:
0.00
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0119
Gnomad4 AMR exome
AF:
0.000696
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000549
Gnomad4 OTH exome
AF:
0.000729
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00293
AC:
445
AN:
152126
Hom.:
4
Cov.:
32
AF XY:
0.00273
AC XY:
203
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0104
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00111
Hom.:
0
Bravo
AF:
0.00335
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 09, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
12
Dann
Benign
0.66
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34515007; hg19: chr15-68378697; COSMIC: COSV51033466; API