chr8-102265232-A-T

Position:

• chr8-102265232-A-T

Variant summary

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

The NM_015902.6(UBR5):​c.7469T>A​(p.Met2490Lys) variant causes a missense change involving the alteration of a conserved nucleotide. 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: UBR5 NM_015902.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

Genes affected

UBR5 (HGNC:16806): (ubiquitin protein ligase E3 component n-recognin 5) This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene is localized to chromosome 8q22 which is disrupted in a variety of cancers. This gene potentially has a role in regulation of cell proliferation or differentiation. [provided by RefSeq, Jul 2008]

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	Protein	UniProt
UBR5	NM_015902.6	c.7469T>A	p.Met2490Lys	missense_variant	53/59	ENST00000520539.6	NP_056986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR5	ENST00000520539.6	c.7469T>A	p.Met2490Lys	missense_variant	53/59	1	NM_015902.6	ENSP00000429084.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Sep 03, 2024

The c.7469T>A (p.M2490K) alteration is located in exon 53 (coding exon 53) of the UBR5 gene. This alteration results from a T to A substitution at nucleotide position 7469, causing the methionine (M) at amino acid position 2490 to be replaced by a lysine (K). 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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T;.;T;.
Eigen	Benign	-0.0035
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.36	N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.73	T;T;T;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.37	B;.;.;P
Vest4		0.77
MutPred		0.47		Loss of stability (P = 0.0026);.;.;.;
MVP		0.47
MPC		2.1
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.38
gMVP		0.64

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: chr8-103277460;