rs1268175928

Variant names:

• chr1-1267929-G-A
• rs1268175928
• NM_058167.3:c.64C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-1267929-G-A
• chr1-1267929-G-C

Variant summary

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

The NM_058167.3(UBE2J2):​c.64C>T​(p.Leu22Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L22V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UBE2J2 NM_058167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.60

Genes affected

UBE2J2 (HGNC:19268): (ubiquitin conjugating enzyme E2 J2) 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 E2 ubiquitin-conjugating enzyme family. This enzyme is located in the membrane of the endoplasmic reticulum. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2J2	NM_058167.3	c.64C>T	p.Leu22Phe	missense_variant	Exon 2 of 7	ENST00000349431.11	NP_477515.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2J2	ENST00000349431.11	c.64C>T	p.Leu22Phe	missense_variant	Exon 2 of 7	1	NM_058167.3	ENSP00000305826.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727194

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;.;T;T;.;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	.;T;T;T;T;T;T
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.2	M;M;M;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D
REVEL	Benign	0.22
Sift	Benign	0.032	D;D;D;T;T;T;D
Sift4G	Benign	0.092	T;T;T;T;.;T;.
Polyphen		0.97	D;D;.;.;.;.;.
Vest4		0.73
MutPred		0.36		Loss of MoRF binding (P = 0.1171);Loss of MoRF binding (P = 0.1171);Loss of MoRF binding (P = 0.1171);Loss of MoRF binding (P = 0.1171);Loss of MoRF binding (P = 0.1171);Loss of MoRF binding (P = 0.1171);Loss of MoRF binding (P = 0.1171);
MVP		0.67
MPC		1.8
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.88
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1268175928; hg19: chr1-1203309; COSMIC: COSV59574004; COSMIC: COSV59574004;