NM_175748.4:c.574T>C

Variant names:

• chr14-93215254-T-C
• rs1016007578
• NM_175748.4:c.574T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_175748.4(UBR7):​c.574T>C​(p.Leu192Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,432,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: UBR7 NM_175748.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 14-93215254-T-C is Benign according to our data. Variant chr14-93215254-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2644476.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.049 with no splicing effect.

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.574T>C	p.Leu192Leu	synonymous	Exon 6 of 11	NP_786924.2	Q8N806
	UBR7	NR_038150.2		n.476T>C		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	ENST00000013070.11	TSL:1 MANE Select	c.574T>C	p.Leu192Leu	synonymous	Exon 6 of 11	ENSP00000013070.6	Q8N806
	UBR7	ENST00000966805.1		c.607T>C	p.Leu203Leu	synonymous	Exon 6 of 11	ENSP00000636864.1
	UBR7	ENST00000940497.1		c.574T>C	p.Leu192Leu	synonymous	Exon 6 of 11	ENSP00000610556.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000349 AC: 5 AN: 1432838 Hom.: 0 Cov.: 31 AF XY: 0.00000423 AC XY: 3 AN XY: 709676

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 39882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25448

East Asian (EAS) AF: 0.00 AC: 0 AN: 39006

South Asian (SAS) AF: 0.00 AC: 0 AN: 81884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1096632

Other (OTH) AF: 0.00 AC: 0 AN: 59386

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.8
DANN	Benign	0.85
PhyloP100		0.049

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: rs1016007578; hg19: chr14-93681600;