15-68141758-TTTG-TTTGTTG

Variant names:

• chr15-68141758-T-TTTG
• rs148686568
• NM_016166.3:c.470-185_470-183dupGTT

Variant summary

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

The NM_016166.3(PIAS1):​c.470-185_470-183dupGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• 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 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.470-185_470-183dupGTT		intron	N/A	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.476-185_476-183dupGTT		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.470-188_470-187insTTG		intron	N/A	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.470-188_470-187insTTG		intron	N/A	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.572-188_572-187insTTG		intron	N/A	ENSP00000569796.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs148686568; hg19: chr15-68434096;