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GeneBe

15-68086518-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_016166.3(PIAS1):c.237C>T(p.Asn79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,613,758 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 1 hom. )

Consequence

PIAS1
NM_016166.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.197
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-68086518-C-T is Benign according to our data. Variant chr15-68086518-C-T is described in ClinVar as [Benign]. Clinvar id is 787960.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=0.197 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 537 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIAS1NM_016166.3 linkuse as main transcriptc.237C>T p.Asn79= synonymous_variant 2/14 ENST00000249636.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIAS1ENST00000249636.11 linkuse as main transcriptc.237C>T p.Asn79= synonymous_variant 2/141 NM_016166.3 P1O75925-1
PIAS1ENST00000545237.1 linkuse as main transcriptc.243C>T p.Asn81= synonymous_variant 3/152 O75925-2
PIAS1ENST00000564915.5 linkuse as main transcriptc.237C>T p.Asn79= synonymous_variant, NMD_transcript_variant 2/55
PIAS1ENST00000562190.1 linkuse as main transcriptc.*327C>T 3_prime_UTR_variant, NMD_transcript_variant 4/63

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00353
AC:
537
AN:
152136
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0113
Gnomad AMI
AF:
0.0230
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.00112
AC:
280
AN:
249138
Hom.:
0
AF XY:
0.000940
AC XY:
127
AN XY:
135142
show subpopulations
Gnomad AFR exome
AF:
0.0149
Gnomad AMR exome
AF:
0.000261
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000168
Gnomad OTH exome
AF:
0.000661
GnomAD4 exome
AF:
0.000495
AC:
723
AN:
1461504
Hom.:
1
Cov.:
32
AF XY:
0.000451
AC XY:
328
AN XY:
727048
show subpopulations
Gnomad4 AFR exome
AF:
0.0128
Gnomad4 AMR exome
AF:
0.000335
Gnomad4 ASJ exome
AF:
0.00161
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000156
Gnomad4 OTH exome
AF:
0.000845
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00356
AC:
542
AN:
152254
Hom.:
2
Cov.:
32
AF XY:
0.00337
AC XY:
251
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0114
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00149
Hom.:
1
Bravo
AF:
0.00397
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

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 testingInvitaeJan 13, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
11
Dann
Benign
0.70
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: rs34057488; hg19: chr15-68378856; API