rs895374

Variant names:

• chr19-58555551-A-C
• rs895374
• NM_003969.4:c.*538T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-58555551-A-C
• chr19-58555551-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003969.4(UBE2M):​c.*538T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,982 control chromosomes in the GnomAD database, including 38,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (38051 hom., cov: 32)
• Consequence: UBE2M NM_003969.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 9 publications found

Genes affected

UBE2M (HGNC:12491): (ubiquitin conjugating enzyme E2 M) 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. The encoded protein is linked with a ubiquitin-like protein, NEDD8, which can be conjugated to cellular proteins, such as Cdc53/culin. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003969.4. 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
	UBE2M	NM_003969.4	MANE Select	c.*538T>G		downstream_gene	N/A	NP_003960.1	A0A024R4T4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2M	ENST00000253023.8	TSL:1 MANE Select	c.*538T>G		downstream_gene	N/A	ENSP00000253023.2	P61081-1
	UBE2M	ENST00000940562.1		c.*538T>G		downstream_gene	N/A	ENSP00000610621.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105356 AN: 151864 Hom.: 37989 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.694 AC: 105476 AN: 151982 Hom.: 38051 Cov.: 32 AF XY: 0.696 AC XY: 51673 AN XY: 74280

African (AFR) AF: 0.899 AC: 37288 AN: 41488

American (AMR) AF: 0.695 AC: 10622 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1806 AN: 3462

East Asian (EAS) AF: 0.796 AC: 4101 AN: 5154

South Asian (SAS) AF: 0.652 AC: 3145 AN: 4820

European-Finnish (FIN) AF: 0.657 AC: 6927 AN: 10542

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39484 AN: 67910

Other (OTH) AF: 0.643 AC: 1357 AN: 2112

Alfa AF: 0.661 Hom.: 10061

Bravo AF: 0.704

Asia WGS AF: 0.784 AC: 2723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.72
PhyloP100		-1.1
PromoterAI		0.049	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs895374; hg19: chr19-59066918;