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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L20W) has been classified as Uncertain significance.

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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Li-Campeau syndrome
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

UBR7 links:

ENSG00000259066 (HGNC:):

ENSG00000259066 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.764

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175748.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	NM_175748.4	MANE Select	c.59T>C	p.Leu20Ser	missense	Exon 1 of 11	NP_786924.2	Q8N806
	UBR7	NR_038150.2		n.95T>C		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBR7	ENST00000013070.11	TSL:1 MANE Select	c.59T>C	p.Leu20Ser	missense	Exon 1 of 11	ENSP00000013070.6	Q8N806
ENSG00000259066	ENST00000557574.1	TSL:4	c.208-2474T>C		intron	N/A	ENSP00000451369.1	G3V3Q6
UBR7	ENST00000966805.1		c.59T>C	p.Leu20Ser	missense	Exon 1 of 11	ENSP00000636864.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000616

AC:

AN:

162468

AF XY:

0.0000116

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 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

African (AFR)

AF:

0.00

AC:

AN:

31924

American (AMR)

AF:

0.00

AC:

AN:

36582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25092

East Asian (EAS)

AF:

0.00

AC:

AN:

36568

South Asian (SAS)

AF:

0.00

AC:

AN:

79730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1082938

Other (OTH)

AF:

0.00

AC:

AN:

58188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.89

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.76

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.6

PhyloP100

6.5

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.88

MutPred

0.30

Gain of phosphorylation at L20 (P = 0.0207)

MVP

0.84

MPC

1.6

ClinPred

0.99

GERP RS

5.0

PromoterAI

0.057

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.81

gMVP

0.95

Mutation Taster

=35/65

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over