19-29942649-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_003796.3(URI1):​c.102C>A​(p.Arg34Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000771 in 1,296,572 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R34R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: URI1 NM_003796.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=-0.308 with no splicing effect.

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>A	p.Arg34Arg	synonymous	Exon 1 of 11	NP_003787.2	O94763-1
	URI1	NM_001252641.2		c.63+18895C>A		intron	N/A	NP_001239570.1	O94763-4
	URI1	NR_045557.1		n.411C>A		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>A	p.Arg34Arg	synonymous	Exon 1 of 11	ENSP00000376097.2	O94763-1
	URI1	ENST00000360605.8	TSL:1	c.63+18895C>A		intron	N/A	ENSP00000353817.4	O94763-4
	URI1	ENST00000574110.5	TSL:1	n.102C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000461003.1	I3L467

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.71e-7 AC: 1 AN: 1296572 Hom.: 0 Cov.: 33 AF XY: 0.00000156 AC XY: 1 AN XY: 641858

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26526

American (AMR) AF: 0.00 AC: 0 AN: 25978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20374

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

South Asian (SAS) AF: 0.0000152 AC: 1 AN: 65974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4226

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1033376

Other (OTH) AF: 0.00 AC: 0 AN: 52406

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		-0.31
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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;