14-93207314-C-T

Variant names:

• chr14-93207314-C-T
• rs149784475
• NM_175748.4:c.23C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175748.4(UBR7):​c.23C>T​(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000712 in 1,405,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. A8D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: UBR7 NM_175748.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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]

ENSG00000259066 (HGNC:):

GON7 (HGNC:20356): (GON7 subunit of KEOPS complex) Located in cytosol; nucleolus; and nucleoplasm. Part of EKC/KEOPS complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13661638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR7	NM_175748.4	c.23C>T	p.Ala8Val	missense_variant	Exon 1 of 11	ENST00000013070.11	NP_786924.2
UBR7	NR_038150.2	n.59C>T		non_coding_transcript_exon_variant	Exon 1 of 10
GON7	NM_032490.5	c.-277G>A		upstream_gene_variant		ENST00000306954.5	NP_115879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR7	ENST00000013070.11	c.23C>T	p.Ala8Val	missense_variant	Exon 1 of 11	1	NM_175748.4	ENSP00000013070.6
ENSG00000259066	ENST00000557574.1	c.208-2510C>T		intron_variant	Intron 2 of 4	4		ENSP00000451369.1
GON7	ENST00000306954.5	c.-277G>A		upstream_gene_variant		1	NM_032490.5	ENSP00000306320.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000712 AC: 10 AN: 1405144 Hom.: 0 Cov.: 33 AF XY: 0.00000865 AC XY: 6 AN XY: 693612

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: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000739

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0096	T;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.044	N
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.73	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.19	T;T;D
Sift4G	Benign	0.10	T;T;T
Polyphen		0.22	B;.;.
Vest4		0.17
MutPred		0.14		Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);
MVP		0.55
MPC		0.50
ClinPred		0.23	T
GERP RS		4.3
Varity_R		0.11
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs149784475; hg19: chr14-93673659;