Variant 19-4013278-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP4_StrongBP6BS2

The NM_015897.4(PIAS4):c.383A>T(p.Lys128Met) variant causes a missense change. The variant allele was found at a frequency of 0.00175 in 1,613,306 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

PIAS4
NM_015897.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.45

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]

PIAS4 links:

PIAS4 (HGNC:):

PIAS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM1

In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) (size 0) in uniprot entity PIAS4_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.01751402).

BP6

Variant 19-4013278-A-T is Benign according to our data. Variant chr19-4013278-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048197.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 163 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIAS4	NM_015897.4 linkuse as main transcript	c.383A>T	p.Lys128Met	missense_variant	2/11	ENST00000262971.3	NP_056981.2
PIAS4	XM_011528060.3 linkuse as main transcript	c.440A>T	p.Lys147Met	missense_variant	2/11		XP_011526362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIAS4	ENST00000262971.3 linkuse as main transcript	c.383A>T	p.Lys128Met	missense_variant	2/11	1	NM_015897.4	ENSP00000262971.1	Q8N2W9
PIAS4	ENST00000593518.1 linkuse as main transcript	n.386A>T		non_coding_transcript_exon_variant	2/3	4
PIAS4	ENST00000599999.5 linkuse as main transcript	n.390A>T		non_coding_transcript_exon_variant	2/4	3
PIAS4	ENST00000600566.5 linkuse as main transcript	n.388A>T		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00122

AC:

307

AN:

250734

Hom.:

AF XY:

0.00136

AC XY:

184

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00337

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00182

AC:

2665

AN:

1461012

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1296

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00359

Gnomad4 NFE exome

AF:

0.00207

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152294

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.000986

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00102

AC:

124

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PIAS4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.038

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.0

REVEL

Benign

0.26

Sift

Uncertain

0.010

Sift4G

Uncertain

0.047

Polyphen

0.58

Vest4

0.52

MVP

0.40

MPC

1.9

ClinPred

0.023

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over