rs2289863

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_015897.4(PIAS4):ā€‹c.738C>Gā€‹(p.Thr246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 30)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

PIAS4
NM_015897.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.881
Variant links:
Genes affected
PIAS4 (HGNC:17002): (protein inhibitor of activated STAT 4) Enables SUMO ligase activity and ubiquitin protein ligase binding activity. Involved in negative regulation of transcription, DNA-templated; positive regulation of protein sumoylation; and protein sumoylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP7
Synonymous conserved (PhyloP=-0.881 with no splicing effect.
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIAS4NM_015897.4 linkuse as main transcriptc.738C>G p.Thr246= synonymous_variant 6/11 ENST00000262971.3
PIAS4XM_011528060.3 linkuse as main transcriptc.795C>G p.Thr265= synonymous_variant 6/11
PIAS4XM_017026868.2 linkuse as main transcriptc.165C>G p.Thr55= synonymous_variant 3/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIAS4ENST00000262971.3 linkuse as main transcriptc.738C>G p.Thr246= synonymous_variant 6/111 NM_015897.4 P1
PIAS4ENST00000596144.1 linkuse as main transcriptn.586C>G non_coding_transcript_exon_variant 5/53
PIAS4ENST00000601439.1 linkuse as main transcriptn.206C>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151810
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461318
Hom.:
0
Cov.:
56
AF XY:
0.00000413
AC XY:
3
AN XY:
726968
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151810
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74130
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
8.8
DANN
Benign
0.61

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: rs2289863; hg19: chr19-4028783; API