3-49808028-G-C

Variant names:

• chr3-49808028-G-C
• rs751934856
• NM_003335.3:c.2515C>G

Variant summary

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

The NM_003335.3(UBA7):​c.2515C>G​(p.Arg839Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. 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: 0.484
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

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.2515C>G	p.Arg839Gly	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.2515C>G	p.Arg839Gly	missense	Exon 20 of 24	ENSP00000333266.3	P41226
	UBA7	ENST00000905619.1		c.2530C>G	p.Arg844Gly	missense	Exon 20 of 24	ENSP00000575678.1
	UBA7	ENST00000905599.1		c.2515C>G	p.Arg839Gly	missense	Exon 21 of 25	ENSP00000575658.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.091
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		0.48
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.38
MutPred		0.76		Loss of MoRF binding (P = 0.034)
MVP		0.33
MPC		0.84
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.77
gMVP		0.69
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs751934856; hg19: chr3-49845461;