chr19-30009211-GTGATGA-G

Variant names:

• chr19-30009211-GTGATGA-G
• rs3840928
• NM_003796.3:c.915_920delTGATGA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_003796.3(URI1):​c.915_920delTGATGA​(p.Asp306_Asp307del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00296 in 1,445,066 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0031 (7 hom.)
• Consequence: URI1 NM_003796.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• 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: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003796.3
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.915_920delTGATGA	p.Asp306_Asp307del	disruptive_inframe_deletion	Exon 8 of 11	NP_003787.2	O94763-1
	URI1	NM_001252641.2		c.861_866delTGATGA	p.Asp288_Asp289del	disruptive_inframe_deletion	Exon 8 of 11	NP_001239570.1	O94763-4
	URI1	NR_045557.1		n.1189_1194delTGATGA		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.915_920delTGATGA	p.Asp306_Asp307del	disruptive_inframe_deletion	Exon 8 of 11	ENSP00000376097.2	O94763-1
	URI1	ENST00000360605.8	TSL:1	c.861_866delTGATGA	p.Asp288_Asp289del	disruptive_inframe_deletion	Exon 8 of 11	ENSP00000353817.4	O94763-4
	URI1	ENST00000574110.5	TSL:1	n.*748_*753delTGATGA		non_coding_transcript_exon	Exon 7 of 10	ENSP00000461003.1	I3L467

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 274 AN: 150588 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000831

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00579

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.000965

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00341

GnomAD2 exomes AF: 0.00451 AC: 953 AN: 211522 AF XY: 0.00438

Gnomad AFR exome AF: 0.00159

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00763

Gnomad EAS exome AF: 0.00187

Gnomad FIN exome AF: 0.00574

Gnomad NFE exome AF: 0.00587

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00309 AC: 3998 AN: 1294358 Hom.: 7 AF XY: 0.00297 AC XY: 1909 AN XY: 643664

African (AFR) AF: 0.000662 AC: 21 AN: 31702

American (AMR) AF: 0.00308 AC: 122 AN: 39626

Ashkenazi Jewish (ASJ) AF: 0.00647 AC: 147 AN: 22714

East Asian (EAS) AF: 0.00141 AC: 50 AN: 35536

South Asian (SAS) AF: 0.000700 AC: 53 AN: 75762

European-Finnish (FIN) AF: 0.00349 AC: 159 AN: 45600

Middle Eastern (MID) AF: 0.000560 AC: 3 AN: 5358

European-Non Finnish (NFE) AF: 0.00334 AC: 3286 AN: 984454

Other (OTH) AF: 0.00293 AC: 157 AN: 53606

GnomAD4 genome AF: 0.00182 AC: 274 AN: 150708 Hom.: 2 Cov.: 0 AF XY: 0.00178 AC XY: 131 AN XY: 73564

African (AFR) AF: 0.000829 AC: 34 AN: 41016

American (AMR) AF: 0.00172 AC: 26 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.00579 AC: 20 AN: 3454

East Asian (EAS) AF: 0.000392 AC: 2 AN: 5096

South Asian (SAS) AF: 0.000422 AC: 2 AN: 4744

European-Finnish (FIN) AF: 0.000965 AC: 10 AN: 10364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00256 AC: 173 AN: 67642

Other (OTH) AF: 0.00338 AC: 7 AN: 2074

Alfa AF: 0.0255 Hom.: 4812

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.4
Mutation Taster		=187/13	polymorphism

Splicing

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: COSV104412958; COSMIC: COSV104412958;