19-29923724-C-A

Position:

• chr19-29923724-C-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001252641.2(URI1):​c.33C>A​(p.His11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: URI1 NM_001252641.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.73

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]

URI1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06463316).
• BP6: Variant 19-29923724-C-A is Benign according to our data. Variant chr19-29923724-C-A is described in ClinVar as [Benign]. Clinvar id is 208948.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
URI1	NM_001252641.2	c.33C>A	p.His11Gln	missense_variant	1/11		NP_001239570.1
URI1	XM_005259362.3	c.33C>A	p.His11Gln	missense_variant	1/11		XP_005259419.1
URI1	XM_011527435.3	c.-23C>A		5_prime_UTR_variant	1/10		XP_011525737.1
URI1	XM_047439595.1	c.-199C>A		5_prime_UTR_variant	1/11		XP_047295551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
URI1	ENST00000360605.8	c.33C>A	p.His11Gln	missense_variant	1/11	1		ENSP00000353817.4
URI1	ENST00000574233.5	c.-238C>A		5_prime_UTR_variant	1/6	3		ENSP00000458480.1
URI1	ENST00000570564.5	c.-348C>A		5_prime_UTR_variant	1/5	4		ENSP00000459966.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1384436 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683124

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Abnormality of neuronal migration Benign:1

Benign, no assertion criteria provided

clinical testing

Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire

Oct 31, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0080
DANN	Benign	0.50
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
REVEL	Benign	0.021
Sift4G	Benign	0.093	T
Vest4		0.060
MVP		0.12
ClinPred		0.041	T
GERP RS		-4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs756055523; hg19: chr19-30414631;