chr19-4028785-C-T

Variant names:

• chr19-4028785-C-T
• rs2289863
• NM_015897.4:c.738C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PIAS4	NM_015897.4	c.738C>T	p.Thr246Thr	synonymous_variant	Exon 6 of 11	ENST00000262971.3	NP_056981.2
PIAS4	XM_011528060.3	c.795C>T	p.Thr265Thr	synonymous_variant	Exon 6 of 11		XP_011526362.1
PIAS4	XM_017026868.2	c.165C>T	p.Thr55Thr	synonymous_variant	Exon 3 of 8		XP_016882357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIAS4	ENST00000262971.3	c.738C>T	p.Thr246Thr	synonymous_variant	Exon 6 of 11	1	NM_015897.4	ENSP00000262971.1
PIAS4	ENST00000596144.1	n.586C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	3
PIAS4	ENST00000601439.1	n.206C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
PIAS4	ENST00000599999.5	n.*198C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90058 AN: 151734 Hom.: 31068 Cov.: 30

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

GnomAD2 exomes AF: 0.709 AC: 177396 AN: 250208 AF XY: 0.711

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 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.: 56 AF XY: 0.728 AC XY: 529199 AN XY: 726942

African (AFR) AF: 0.185 AC: 6195 AN: 33476

American (AMR) AF: 0.805 AC: 35983 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 17939 AN: 26126

East Asian (EAS) AF: 0.899 AC: 35686 AN: 39690

South Asian (SAS) AF: 0.641 AC: 55259 AN: 86252

European-Finnish (FIN) AF: 0.700 AC: 37058 AN: 52972

Middle Eastern (MID) AF: 0.609 AC: 3512 AN: 5768

European-Non Finnish (NFE) AF: 0.748 AC: 831885 AN: 1111882

Other (OTH) AF: 0.710 AC: 42842 AN: 60382

GnomAD4 genome AF: 0.593 AC: 90082 AN: 151852 Hom.: 31079 Cov.: 30 AF XY: 0.597 AC XY: 44283 AN XY: 74224

African (AFR) AF: 0.210 AC: 8717 AN: 41422

American (AMR) AF: 0.721 AC: 11002 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2415 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4670 AN: 5124

South Asian (SAS) AF: 0.651 AC: 3137 AN: 4818

European-Finnish (FIN) AF: 0.708 AC: 7466 AN: 10544

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50459 AN: 67920

Other (OTH) AF: 0.610 AC: 1283 AN: 2104

Alfa AF: 0.691 Hom.: 78762

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
PhyloP100		-0.88
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289863; hg19: chr19-4028783; COSMIC: COSV108078769; COSMIC: COSV108078769;