1-145851056-A-G

Variant names:

• chr1-145851056-A-G
• NM_006099.3:c.1243T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006099.3(PIAS3):​c.1243T>C​(p.Ser415Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIAS3 NM_006099.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23
• Publications: 0 publications found

Genes affected

PIAS3 (HGNC:16861): (protein inhibitor of activated STAT 3) This gene encodes a member of the PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] family of transcriptional modulators. The protein functions as a SUMO (small ubiquitin-like modifier)-E3 ligase which catalyzes the covalent attachment of a SUMO protein to specific target substrates. It directly binds to several transcription factors and either blocks or enhances their activity. Alternatively spliced transcript variants of this gene have been identified, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12710977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006099.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIAS3	NM_006099.3	MANE Select	c.1243T>C	p.Ser415Pro	missense	Exon 10 of 14	NP_006090.2	Q9Y6X2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIAS3	ENST00000393045.7	TSL:1 MANE Select	c.1243T>C	p.Ser415Pro	missense	Exon 10 of 14	ENSP00000376765.2	Q9Y6X2
	PIAS3	ENST00000475261.1	TSL:1	n.1111T>C		non_coding_transcript_exon	Exon 3 of 7
	PIAS3	ENST00000948928.1		c.1243T>C	p.Ser415Pro	missense	Exon 10 of 14	ENSP00000618987.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.13	T
PhyloP100		5.2
PROVEAN	Benign	-0.72	N
Sift	Benign	0.19	T
Sift4G	Benign	0.32	T
Vest4		0.065
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr1-145584012;