dbSNP rs1209467085: UBR7:p.Leu20Ser (chr14-93207350-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_175748.4(UBR7):c.59T>C(p.Leu20Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,406,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBR7
NM_175748.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.50

Variant links:

Genes affected

UBR7 (HGNC:20344): (ubiquitin protein ligase E3 component n-recognin 7) This gene encodes a UBR box-containing protein that belongs to the E3 ubiquitin ligase family. The protein also contains a plant homeodomain (PHD) in the C-terminus. In mammals, the encoded protein recognizes N-degrons, the destabilizing N-terminal residues of short-lived proteins, which results in ubiquitinylation, and proteolysis via the proteasome. [provided by RefSeq, Jul 2016]

UBR7 links:

ENSG00000259066 (HGNC:):

ENSG00000259066 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR7	NM_175748.4 link	c.59T>C	p.Leu20Ser	missense_variant	Exon 1 of 11	ENST00000013070.11	NP_786924.2
UBR7	NR_038150.2 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR7	ENST00000013070.11 link	c.59T>C	p.Leu20Ser	missense_variant	Exon 1 of 11	1	NM_175748.4	ENSP00000013070.6		Q8N806
ENSG00000259066	ENST00000557574.1 link	c.208-2474T>C		intron_variant	Intron 2 of 4	4		ENSP00000451369.1		G3V3Q6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000616

AC:

AN:

162468

Hom.:

AF XY:

0.0000116

AC XY:

AN XY:

86448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1406142

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694166

show subpopulations

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:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.89

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.6

M;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.5

D;D;N

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.88

MutPred

0.30

Gain of phosphorylation at L20 (P = 0.0207);Gain of phosphorylation at L20 (P = 0.0207);Gain of phosphorylation at L20 (P = 0.0207);

MVP

0.84

MPC

1.6

ClinPred

0.99

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.81

gMVP

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over