rs1266883583

Variant names:

• chr19-29942591-C-A
• NM_003796.3:c.44C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-29942591-C-A
• chr19-29942591-C-G
• chr19-29942591-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003796.3(URI1):​c.44C>A​(p.Pro15His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000778 in 1,285,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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. P15L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: URI1 NM_003796.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039533883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
URI1	NM_003796.3	c.44C>A	p.Pro15His	missense_variant	Exon 1 of 11	ENST00000392271.6	NP_003787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
URI1	ENST00000392271.6	c.44C>A	p.Pro15His	missense_variant	Exon 1 of 11	1	NM_003796.3	ENSP00000376097.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.78e-7 AC: 1 AN: 1285128 Hom.: 0 Cov.: 33 AF XY: 0.00000158 AC XY: 1 AN XY: 634018

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.69e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.1
DANN	Benign	0.50
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.75	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.099
MutPred		0.20		Loss of glycosylation at P15 (P = 0.0027);
MVP		0.36
ClinPred		0.027	T
GERP RS		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.032
gMVP		0.27

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-30433498;