chr19-30009211-G-GTGA

Variant names:

• chr19-30009211-G-GTGA
• rs3840928
• NM_003796.3:c.918_920dupTGA

Variant summary

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

The NM_003796.3(URI1):​c.918_920dupTGA​(p.Asp307dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D307D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 0)
  • Exomes 𝑓: 0.00060 (3 hom.)
• Consequence: URI1 NM_003796.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• 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 4 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.918_920dupTGA	p.Asp307dup	disruptive_inframe_insertion	Exon 8 of 11	NP_003787.2	O94763-1
	URI1	NM_001252641.2		c.864_866dupTGA	p.Asp289dup	disruptive_inframe_insertion	Exon 8 of 11	NP_001239570.1	O94763-4
	URI1	NR_045557.1		n.1192_1194dupTGA		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_920dupTGA	p.Asp307dup	disruptive_inframe_insertion	Exon 8 of 11	ENSP00000376097.2	O94763-1
	URI1	ENST00000360605.8	TSL:1	c.864_866dupTGA	p.Asp289dup	disruptive_inframe_insertion	Exon 8 of 11	ENSP00000353817.4	O94763-4
	URI1	ENST00000574110.5	TSL:1	n.*751_*753dupTGA		non_coding_transcript_exon	Exon 7 of 10	ENSP00000461003.1	I3L467

Frequencies

GnomAD3 genomes AF: 0.00416 AC: 627 AN: 150682 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00225

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00243

GnomAD2 exomes AF: 0.00168 AC: 355 AN: 211522 AF XY: 0.00132

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000644

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000298

Gnomad OTH exome AF: 0.000765

GnomAD4 exome AF: 0.000599 AC: 833 AN: 1390736 Hom.: 3 Cov.: 0 AF XY: 0.000582 AC XY: 403 AN XY: 692174

African (AFR) AF: 0.0139 AC: 455 AN: 32768

American (AMR) AF: 0.00117 AC: 50 AN: 42882

Ashkenazi Jewish (ASJ) AF: 0.0000401 AC: 1 AN: 24930

East Asian (EAS) AF: 0.000131 AC: 5 AN: 38196

South Asian (SAS) AF: 0.000897 AC: 74 AN: 82518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50318

Middle Eastern (MID) AF: 0.00125 AC: 7 AN: 5604

European-Non Finnish (NFE) AF: 0.000171 AC: 181 AN: 1055884

Other (OTH) AF: 0.00104 AC: 60 AN: 57636

GnomAD4 genome AF: 0.00415 AC: 626 AN: 150802 Hom.: 4 Cov.: 0 AF XY: 0.00389 AC XY: 286 AN XY: 73606

African (AFR) AF: 0.0140 AC: 574 AN: 41016

American (AMR) AF: 0.00225 AC: 34 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5098

South Asian (SAS) AF: 0.000422 AC: 2 AN: 4742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10404

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67688

Other (OTH) AF: 0.00241 AC: 5 AN: 2076

Alfa AF: 0.000614 Hom.: 4812

Bravo AF: 0.00499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42
Mutation Taster		=77/23	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;