1-229635716-C-A

Position:

• chr1-229635716-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014777.4(URB2):​c.1103C>A​(p.Ala368Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: URB2 NM_014777.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43

Genes affected

URB2 (HGNC:28967): (URB2 ribosome biogenesis homolog) Predicted to be involved in ribosome biogenesis. Located in aggresome; midbody; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
URB2	NM_014777.4	c.1103C>A	p.Ala368Asp	missense_variant	4/10	ENST00000258243.7
URB2	NM_001314021.2	c.1103C>A	p.Ala368Asp	missense_variant	4/10
URB2	XM_005273360.3	c.1103C>A	p.Ala368Asp	missense_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
URB2	ENST00000258243.7	c.1103C>A	p.Ala368Asp	missense_variant	4/10	1	NM_014777.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2023

The c.1103C>A (p.A368D) alteration is located in exon 4 (coding exon 3) of the URB2 gene. This alteration results from a C to A substitution at nucleotide position 1103, causing the alanine (A) at amino acid position 368 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.78	D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.21
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.53
MutPred		0.47		Loss of helix (P = 0.0167);
MVP		0.53
MPC		0.29
ClinPred		0.85	D
GERP RS		3.1
Varity_R		0.20
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs1571869907; hg19: chr1-229771463;