15-68141874-T-TGTG

Variant names:

• chr15-68141874-T-TGTG
• rs113300929
• NM_016166.3:c.470-72_470-71insGTG

Variant summary

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

The NM_016166.3(PIAS1):​c.470-72_470-71insGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000034 in 588,170 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.470-72_470-71insGTG		intron	N/A	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.476-72_476-71insGTG		intron	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.470-72_470-71insGTG		intron	N/A	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.470-72_470-71insGTG		intron	N/A	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.572-72_572-71insGTG		intron	N/A	ENSP00000569796.1

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145740 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000684

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: 0.00000226 AC: 1 AN: 442430 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 228508

African (AFR) AF: 0.00 AC: 0 AN: 11216

American (AMR) AF: 0.00 AC: 0 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12596

East Asian (EAS) AF: 0.00 AC: 0 AN: 9022

South Asian (SAS) AF: 0.00 AC: 0 AN: 27918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 312718

Other (OTH) AF: 0.0000458 AC: 1 AN: 21832

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145740 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 70906

African (AFR) AF: 0.00 AC: 0 AN: 39756

American (AMR) AF: 0.0000684 AC: 1 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 4860

South Asian (SAS) AF: 0.00 AC: 0 AN: 4570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66002

Other (OTH) AF: 0.00 AC: 0 AN: 2024

Alfa AF: 0.00 Hom.: 48

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113300929; hg19: chr15-68434212;