14-93210656-G-T

Variant names:

• chr14-93210656-G-T
• rs751474426
• NM_175748.4:c.293G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_175748.4(UBR7):​c.293G>T​(p.Arg98Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R98H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBR7 NM_175748.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

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

ENSG00000259066 (HGNC:):

ACMG classification

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, 0.818

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	NM_175748.4	MANE Select	c.293G>T	p.Arg98Leu	missense	Exon 3 of 11	NP_786924.2
	UBR7	NR_038150.2		n.195G>T		non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	ENST00000013070.11	TSL:1 MANE Select	c.293G>T	p.Arg98Leu	missense	Exon 3 of 11	ENSP00000013070.6
	ENSG00000259066	ENST00000557574.1	TSL:4	c.350G>T	p.Arg117Leu	missense	Exon 4 of 5	ENSP00000451369.1
	UBR7	ENST00000554232.5	TSL:4	c.293G>T	p.Arg98Leu	missense	Exon 3 of 6	ENSP00000450645.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.79
Sift	Benign	0.11	T
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.61		Loss of sheet (P = 0.0457)
MVP		0.77
MPC		1.1
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.92
Mutation Taster		=16/84	disease causing

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

Other links and lift over

dbSNP: rs751474426; hg19: chr14-93677002;