chr15-68054335-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_016166.3(PIAS1):​c.9C>T​(p.Asp3Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000702 in 1,424,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PIAS1 NM_016166.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 15-68054335-C-T is Benign according to our data. Variant chr15-68054335-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2805153.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T	p.Asp3Asp	synonymous	Exon 1 of 14	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.-982C>T		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>T	p.Asp3Asp	synonymous	Exon 1 of 14	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.9C>T	p.Asp3Asp	synonymous	Exon 1 of 15	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.9C>T	p.Asp3Asp	synonymous	Exon 1 of 15	ENSP00000569796.1

Frequencies

GnomAD3 genomes Cov.: 32

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

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: 0.00 AC: 0 AN: 1094130

Other (OTH) AF: 0.0000170 AC: 1 AN: 58970

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		4.1
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;