rs3803341

Variant names:

• chr15-42945005-T-A
• rs3803341
• NM_174916.3:c.*324A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-42945005-T-A
• chr15-42945005-T-C
• chr15-42945005-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174916.3(UBR1):​c.*324A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBR1 NM_174916.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 12 publications found

Genes affected

UBR1 (HGNC:16808): (ubiquitin protein ligase E3 component n-recognin 1) The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008]

UBR1 Gene-Disease associations (from GenCC):

• Johanson-Blizzard syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR1	NM_174916.3	c.*324A>T		3_prime_UTR_variant	Exon 47 of 47	ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9	c.*324A>T		3_prime_UTR_variant	Exon 47 of 47	1	NM_174916.3	ENSP00000290650.4
UBR1	ENST00000562173.1	n.*182A>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 182964 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 98436

African (AFR) AF: 0.00 AC: 0 AN: 5356

American (AMR) AF: 0.00 AC: 0 AN: 7446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4782

East Asian (EAS) AF: 0.00 AC: 0 AN: 8076

South Asian (SAS) AF: 0.00 AC: 0 AN: 32068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 106516

Other (OTH) AF: 0.00 AC: 0 AN: 9422

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 149704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.5
DANN	Benign	0.79
PhyloP100		-0.096

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: rs3803341; hg19: chr15-43237203;