19-30009211-GTGATGATGATGATGA-GTGATGATGATGA

Variant names:

• chr19-30009211-GTGA-G
• rs3840928
• NM_003796.3:c.918_920delTGA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BA1

The NM_003796.3(URI1):​c.918_920delTGA​(p.Asp307del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.83 in 1,540,862 control chromosomes in the GnomAD database, including 526,078 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (49457 hom., cov: 0)
  • Exomes 𝑓: 0.83 (476621 hom.)
• Consequence: URI1 NM_003796.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71
• Publications: 17 publications found

Genes affected

URI1 (HGNC:13236): (URI1 prefoldin like chaperone) This gene encodes member of the prefoldin family of molecular chaperones. The encoded protein functions as a scaffolding protein and plays roles in ubiquitination and transcription, in part though interactions with the RNA polymerase II subunit RPB5. This gene may play a role in multiple malignancies including ovarian cancer and hepatocellular carcinoma. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 22. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003796.3
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003796.3. 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
	URI1	NM_003796.3	MANE Select	c.918_920delTGA	p.Asp307del	disruptive_inframe_deletion	Exon 8 of 11	NP_003787.2	O94763-1
	URI1	NM_001252641.2		c.864_866delTGA	p.Asp289del	disruptive_inframe_deletion	Exon 8 of 11	NP_001239570.1	O94763-4
	URI1	NR_045557.1		n.1192_1194delTGA		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URI1	ENST00000392271.6	TSL:1 MANE Select	c.918_920delTGA	p.Asp307del	disruptive_inframe_deletion	Exon 8 of 11	ENSP00000376097.2	O94763-1
	URI1	ENST00000360605.8	TSL:1	c.864_866delTGA	p.Asp289del	disruptive_inframe_deletion	Exon 8 of 11	ENSP00000353817.4	O94763-4
	URI1	ENST00000574110.5	TSL:1	n.*751_*753delTGA		non_coding_transcript_exon	Exon 7 of 10	ENSP00000461003.1	I3L467

Frequencies

GnomAD3 genomes AF: 0.799 AC: 120298 AN: 150586 Hom.: 49436 Cov.: 0

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.826

GnomAD2 exomes AF: 0.818 AC: 173110 AN: 211522 AF XY: 0.825

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.768

Gnomad ASJ exome AF: 0.878

Gnomad EAS exome AF: 0.712

Gnomad FIN exome AF: 0.897

Gnomad NFE exome AF: 0.872

Gnomad OTH exome AF: 0.833

GnomAD4 exome AF: 0.833 AC: 1158550 AN: 1390154 Hom.: 476621 AF XY: 0.832 AC XY: 575897 AN XY: 691856

African (AFR) AF: 0.559 AC: 18255 AN: 32656

American (AMR) AF: 0.748 AC: 32058 AN: 42844

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 20954 AN: 24926

East Asian (EAS) AF: 0.742 AC: 28280 AN: 38134

South Asian (SAS) AF: 0.777 AC: 64101 AN: 82450

European-Finnish (FIN) AF: 0.860 AC: 43283 AN: 50304

Middle Eastern (MID) AF: 0.766 AC: 4293 AN: 5602

European-Non Finnish (NFE) AF: 0.853 AC: 900728 AN: 1055630

Other (OTH) AF: 0.809 AC: 46598 AN: 57608

GnomAD4 genome AF: 0.799 AC: 120352 AN: 150708 Hom.: 49457 Cov.: 0 AF XY: 0.800 AC XY: 58866 AN XY: 73558

African (AFR) AF: 0.593 AC: 24298 AN: 40970

American (AMR) AF: 0.816 AC: 12331 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3071 AN: 3456

East Asian (EAS) AF: 0.751 AC: 3822 AN: 5092

South Asian (SAS) AF: 0.832 AC: 3941 AN: 4736

European-Finnish (FIN) AF: 0.915 AC: 9523 AN: 10402

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.895 AC: 60541 AN: 67668

Other (OTH) AF: 0.825 AC: 1712 AN: 2074

Alfa AF: 0.704 Hom.: 4812

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=81/19	polymorphism (auto)

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: rs3840928; hg19: chr19-30500118; COSMIC: COSV56347773; COSMIC: COSV56347773;