rs139286220

Variant names:

• chr3-49805385-G-A
• rs139286220
• NM_003335.3:c.2962C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003335.3(UBA7):​c.2962C>T​(p.Arg988Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: UBA7 NM_003335.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.953
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07710025).

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.2962C>T	p.Arg988Trp	missense	Exon 24 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.2962C>T	p.Arg988Trp	missense	Exon 24 of 24	ENSP00000333266.3	P41226
	UBA7	ENST00000905619.1		c.2977C>T	p.Arg993Trp	missense	Exon 24 of 24	ENSP00000575678.1
	UBA7	ENST00000905599.1		c.2962C>T	p.Arg988Trp	missense	Exon 25 of 25	ENSP00000575658.1

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151854 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000322 AC: 8 AN: 248830 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000719

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 173 AN: 1461830 Hom.: 0 Cov.: 32 AF XY: 0.000109 AC XY: 79 AN XY: 727210

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000146 AC: 162 AN: 1112000

Other (OTH) AF: 0.000149 AC: 9 AN: 60394

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151972 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.95
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.080
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.0020	B
Vest4		0.16
MVP		0.13
MPC		0.24
ClinPred		0.14	T
GERP RS		0.81
Varity_R		0.11
gMVP		0.82
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: rs139286220; hg19: chr3-49842818;