rs782819366

Variant names:

• chr1-145849471-C-A
• rs782819366
• NM_006099.3:c.1862G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-145849471-C-A
• chr1-145849471-C-T

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.1862G>T​(p.Arg621Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R621Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PIAS3 NM_006099.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• 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=0.098727286).

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.1862G>T	p.Arg621Leu	missense	Exon 14 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.1862G>T	p.Arg621Leu	missense	Exon 14 of 14	ENSP00000376765.2	Q9Y6X2
	PIAS3	ENST00000475261.1	TSL:1	n.1730G>T		non_coding_transcript_exon	Exon 7 of 7
	PIAS3	ENST00000948928.1		c.1856G>T	p.Arg619Leu	missense	Exon 14 of 14	ENSP00000618987.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356324 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 666270

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29588

American (AMR) AF: 0.00 AC: 0 AN: 27472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19880

East Asian (EAS) AF: 0.00 AC: 0 AN: 37194

South Asian (SAS) AF: 0.00 AC: 0 AN: 69232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5238

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1064632

Other (OTH) AF: 0.00 AC: 0 AN: 55950

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.055	T
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.099	T
PhyloP100		2.5
PROVEAN	Benign	-0.17	N
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.27
gMVP		0.69

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: rs782819366; hg19: chr1-145585597;