rs928724922

Variant names:

• chr15-68054335-C-G
• rs928724922
• NM_016166.3:c.9C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-68054335-C-G
• chr15-68054335-C-T

Variant summary

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

The NM_016166.3(PIAS1):​c.9C>G​(p.Asp3Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000127 in 1,576,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D3D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PIAS1 NM_016166.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09
• Publications: 0 publications found

Genes affected

PIAS1 (HGNC:2752): (protein inhibitor of activated STAT 1) This gene encodes a member of the protein inhibitor of activated STAT (PIAS) family. PIAS proteins function as SUMO E3 ligases and play important roles in many cellular processes by mediating the sumoylation of target proteins. This protein plays a central role as a transcriptional coregulator of numerous cellular pathways includign the STAT1 and nuclear factor kappaB pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

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=0.10265082).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016166.3. 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
	PIAS1	NM_016166.3	MANE Select	c.9C>G	p.Asp3Glu	missense	Exon 1 of 14	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.-982C>G		upstream_gene	N/A	NP_001307616.1	O75925-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIAS1	ENST00000249636.11	TSL:1 MANE Select	c.9C>G	p.Asp3Glu	missense	Exon 1 of 14	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.9C>G	p.Asp3Glu	missense	Exon 1 of 15	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.9C>G	p.Asp3Glu	missense	Exon 1 of 15	ENSP00000569796.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424790 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705544

⚠️ 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: 32310

American (AMR) AF: 0.00 AC: 0 AN: 39878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25432

East Asian (EAS) AF: 0.00 AC: 0 AN: 37238

South Asian (SAS) AF: 0.00 AC: 0 AN: 81192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094130

Other (OTH) AF: 0.00 AC: 0 AN: 58970

⚠️ 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 AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.31
MutPred		0.33		Gain of methylation at K8 (P = 0.0833)
MVP		0.45
MPC		0.55
ClinPred		0.59	D
GERP RS		3.6
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18

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: rs928724922; hg19: chr15-68346673;