19-29942581-C-A

Variant names:

• chr19-29942581-C-A
• rs551935451
• NM_003796.3:c.34C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003796.3(URI1):​c.34C>A​(p.Pro12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000785 in 1,273,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: URI1 NM_003796.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07481867).

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.34C>A	p.Pro12Thr	missense	Exon 1 of 11	NP_003787.2	O94763-1
	URI1	NM_001252641.2		c.63+18827C>A		intron	N/A	NP_001239570.1	O94763-4
	URI1	NR_045557.1		n.343C>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.34C>A	p.Pro12Thr	missense	Exon 1 of 11	ENSP00000376097.2	O94763-1
	URI1	ENST00000360605.8	TSL:1	c.63+18827C>A		intron	N/A	ENSP00000353817.4	O94763-4
	URI1	ENST00000574110.5	TSL:1	n.34C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000461003.1	I3L467

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000170 AC: 1 AN: 58868 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.85e-7 AC: 1 AN: 1273100 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 627066

⚠️ 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: 25416

American (AMR) AF: 0.0000543 AC: 1 AN: 18402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20688

East Asian (EAS) AF: 0.00 AC: 0 AN: 28520

South Asian (SAS) AF: 0.00 AC: 0 AN: 66064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1024806

Other (OTH) AF: 0.00 AC: 0 AN: 51860

⚠️ 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
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.65
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.41	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.084
PrimateAI	Uncertain	0.70	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.57	P
Vest4		0.13
MutPred		0.20		Gain of phosphorylation at P12 (P = 0.0025)
MVP		0.23
ClinPred		0.085	T
GERP RS		2.1
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.054
gMVP		0.36
Mutation Taster		=292/8	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: rs551935451; hg19: chr19-30433488;