19-29942649-C-G

Variant names:

• chr19-29942649-C-G
• rs200928000
• NM_003796.3:c.102C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_003796.3(URI1):​c.102C>G​(p.Arg34Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,448,452 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (83 hom.)
• Consequence: URI1 NM_003796.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.308
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (REVEL=0.039).
• BP6: Variant 19-29942649-C-G is Benign according to our data. Variant chr19-29942649-C-G is described in ClinVar as Benign. ClinVar VariationId is 2649668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.308 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 7 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.102C>G	p.Arg34Arg	synonymous	Exon 1 of 11	NP_003787.2	O94763-1
	URI1	NM_001252641.2		c.63+18895C>G		intron	N/A	NP_001239570.1	O94763-4
	URI1	NR_045557.1		n.411C>G		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URI1	ENST00000392271.6	TSL:1 MANE Select	c.102C>G	p.Arg34Arg	synonymous	Exon 1 of 11	ENSP00000376097.2	O94763-1
	URI1	ENST00000360605.8	TSL:1	c.63+18895C>G		intron	N/A	ENSP00000353817.4	O94763-4
	URI1	ENST00000574110.5	TSL:1	n.102C>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000461003.1	I3L467

Frequencies

GnomAD3 genomes AF: 0.00812 AC: 1234 AN: 151880 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00671

GnomAD2 exomes AF: 0.00936 AC: 1141 AN: 121842 AF XY: 0.00923

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00507

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0217

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.0107

GnomAD4 exome AF: 0.0110 AC: 14241 AN: 1296464 Hom.: 83 Cov.: 33 AF XY: 0.0108 AC XY: 6900 AN XY: 641798

African (AFR) AF: 0.00147 AC: 39 AN: 26522

American (AMR) AF: 0.00531 AC: 138 AN: 25974

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 219 AN: 20370

East Asian (EAS) AF: 0.00 AC: 0 AN: 31096

South Asian (SAS) AF: 0.00276 AC: 182 AN: 65972

European-Finnish (FIN) AF: 0.0237 AC: 867 AN: 36590

Middle Eastern (MID) AF: 0.00402 AC: 17 AN: 4226

European-Non Finnish (NFE) AF: 0.0119 AC: 12275 AN: 1033314

Other (OTH) AF: 0.00962 AC: 504 AN: 52400

GnomAD4 genome AF: 0.00811 AC: 1233 AN: 151988 Hom.: 7 Cov.: 32 AF XY: 0.00863 AC XY: 641 AN XY: 74300

African (AFR) AF: 0.00159 AC: 66 AN: 41530

American (AMR) AF: 0.00628 AC: 96 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.0235 AC: 247 AN: 10518

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0111 AC: 754 AN: 67888

Other (OTH) AF: 0.00664 AC: 14 AN: 2108

Alfa AF: 0.00273 Hom.: 0

Bravo AF: 0.00654

ClinVar

ClinVar submissions

Significance: 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	-0.38
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		-0.31
PromoterAI		-0.12	Neutral
Mutation Taster		=94/6	polymorphism

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: rs200928000; hg19: chr19-30433556; COSMIC: COSV56349307; COSMIC: COSV56349307;