19-4028743-C-T

Variant summary

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

The NM_015897.4(PIAS4):​c.696C>T​(p.Pro232Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,612,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

PIAS4
NM_015897.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.03
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 -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 19-4028743-C-T is Benign according to our data. Variant chr19-4028743-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3888624.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-4.03 with no splicing effect.
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIAS4NM_015897.4 linkc.696C>T p.Pro232Pro synonymous_variant Exon 6 of 11 ENST00000262971.3 NP_056981.2
PIAS4XM_011528060.3 linkc.753C>T p.Pro251Pro synonymous_variant Exon 6 of 11 XP_011526362.1
PIAS4XM_017026868.2 linkc.123C>T p.Pro41Pro synonymous_variant Exon 3 of 8 XP_016882357.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIAS4ENST00000262971.3 linkc.696C>T p.Pro232Pro synonymous_variant Exon 6 of 11 1 NM_015897.4 ENSP00000262971.1 Q8N2W9
PIAS4ENST00000596144.1 linkn.544C>T non_coding_transcript_exon_variant Exon 5 of 5 3
PIAS4ENST00000601439.1 linkn.164C>T non_coding_transcript_exon_variant Exon 2 of 2 3
PIAS4ENST00000599999.5 linkn.*156C>T downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152100
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000844
AC:
21
AN:
248818
Hom.:
0
AF XY:
0.000126
AC XY:
17
AN XY:
134856
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.0000467
Gnomad NFE exome
AF:
0.000116
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000500
AC:
73
AN:
1460310
Hom.:
0
Cov.:
35
AF XY:
0.0000619
AC XY:
45
AN XY:
726398
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.0000569
Gnomad4 NFE exome
AF:
0.0000414
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152100
Hom.:
0
Cov.:
30
AF XY:
0.0000538
AC XY:
4
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000764
Hom.:
0
Bravo
AF:
0.0000529
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Benign:1
Jan 04, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
1.5
DANN
Benign
0.77

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: rs759088793; hg19: chr19-4028741; COSMIC: COSV105021994; COSMIC: COSV105021994; API