3-49808027-C-A

Variant names:

• chr3-49808027-C-A
• rs118020287
• NM_003335.3:c.2516G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003335.3(UBA7):​c.2516G>T​(p.Arg839Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R839P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBA7 NM_003335.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 0 publications found

Genes affected

UBA7 (HGNC:12471): (ubiquitin like modifier activating enzyme 7) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme is a retinoid target that triggers promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) degradation and apoptosis in acute promyelocytic leukemia, where it is involved in the conjugation of the ubiquitin-like interferon-stimulated gene 15 protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003335.3. 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
	UBA7	NM_003335.3	MANE Select	c.2516G>T	p.Arg839Leu	missense	Exon 20 of 24	NP_003326.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA7	ENST00000333486.4	TSL:1 MANE Select	c.2516G>T	p.Arg839Leu	missense	Exon 20 of 24	ENSP00000333266.3	P41226
	UBA7	ENST00000905619.1		c.2531G>T	p.Arg844Leu	missense	Exon 20 of 24	ENSP00000575678.1
	UBA7	ENST00000905599.1		c.2516G>T	p.Arg839Leu	missense	Exon 21 of 25	ENSP00000575658.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.63
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.90	P
Vest4		0.44
MutPred		0.72		Loss of MoRF binding (P = 0.0314)
MVP		0.25
MPC		0.70
ClinPred		0.99	D
GERP RS		-0.67
Varity_R		0.39
gMVP		0.69
Mutation Taster		=100/0	polymorphism

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: rs118020287; hg19: chr3-49845460;