Variant 19-4028785-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_015897.4(PIAS4):c.738C>T(p.Thr246Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,613,108 control chromosomes in the GnomAD database, including 427,523 homozygotes. 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: 𝑓 0.59 ( 31079 hom., cov: 30)

Exomes 𝑓: 0.73 ( 396444 hom. )

Consequence

PIAS4
NM_015897.4 synonymous

Scores

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]

PIAS4 links:

PIAS4 (HGNC:):

PIAS4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=-0.881 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIAS4	NM_015897.4 linkuse as main transcript	c.738C>T	p.Thr246Thr	synonymous_variant	6/11	ENST00000262971.3	NP_056981.2
PIAS4	XM_011528060.3 linkuse as main transcript	c.795C>T	p.Thr265Thr	synonymous_variant	6/11		XP_011526362.1
PIAS4	XM_017026868.2 linkuse as main transcript	c.165C>T	p.Thr55Thr	synonymous_variant	3/8		XP_016882357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIAS4	ENST00000262971.3 linkuse as main transcript	c.738C>T	p.Thr246Thr	synonymous_variant	6/11	1	NM_015897.4	ENSP00000262971.1	Q8N2W9
PIAS4	ENST00000596144.1 linkuse as main transcript	n.586C>T		splice_region_variant, non_coding_transcript_exon_variant	5/5	3
PIAS4	ENST00000601439.1 linkuse as main transcript	n.206C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90058

AN:

151734

Hom.:

31068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.830

Gnomad AMR

AF:

0.721

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.651

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.611

GnomAD3 exomes

AF:

0.709

AC:

177396

AN:

250208

Hom.:

65988

AF XY:

0.711

AC XY:

96395

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.815

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.915

Gnomad SAS exome

AF:

0.639

Gnomad FIN exome

AF:

0.700

Gnomad NFE exome

AF:

0.739

Gnomad OTH exome

AF:

0.710

GnomAD4 exome

AF:

0.730

AC:

1066359

AN:

1461256

Hom.:

396444

Cov.:

AF XY:

0.728

AC XY:

529199

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.687

Gnomad4 EAS exome

AF:

0.899

Gnomad4 SAS exome

AF:

0.641

Gnomad4 FIN exome

AF:

0.700

Gnomad4 NFE exome

AF:

0.748

Gnomad4 OTH exome

AF:

0.710

GnomAD4 genome

AF:

0.593

AC:

90082

AN:

151852

Hom.:

31079

Cov.:

AF XY:

0.597

AC XY:

44283

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.721

Gnomad4 ASJ

AF:

0.696

Gnomad4 EAS

AF:

0.911

Gnomad4 SAS

AF:

0.651

Gnomad4 FIN

AF:

0.708

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.704

Hom.:

60585

Bravo

AF:

0.580

Asia WGS

AF:

0.741

AC:

2574

AN:

3478

EpiCase

AF:

0.721

EpiControl

AF:

0.727

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.4

DANN

Benign

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over