rs7739323

Positions:

• chr6-82957326-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198920.3(UBE3D):​c.1135G>A​(p.Val379Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,612,580 control chromosomes in the GnomAD database, including 19,957 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (1974 hom., cov: 31)
  • Exomes 𝑓: 0.16 (17983 hom.)
• Consequence: UBE3D NM_198920.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

Genes affected

UBE3D (HGNC:21381): (ubiquitin protein ligase E3D) Enables cyclin binding activity; ubiquitin protein ligase activity; and ubiquitin-like protein conjugating enzyme binding activity. Involved in protein autoubiquitination; protein monoubiquitination; and protein polyubiquitination. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002778232).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE3D	NM_198920.3	c.1135G>A	p.Val379Met	missense_variant	9/10	ENST00000369747.8	NP_944602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3D	ENST00000369747.8	c.1135G>A	p.Val379Met	missense_variant	9/10	1	NM_198920.3	ENSP00000358762	P1
UBE3D	ENST00000237186.10	c.*986G>A		3_prime_UTR_variant, NMD_transcript_variant	9/10	1		ENSP00000237186
UBE3D	ENST00000509102.5	c.*254G>A		3_prime_UTR_variant, NMD_transcript_variant	9/10	1		ENSP00000427101
UBE3D	ENST00000430071.6	c.*830G>A		3_prime_UTR_variant, NMD_transcript_variant	10/11	5		ENSP00000394749

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24202 AN: 151880 Hom.: 1971 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.150 AC: 37515 AN: 250862 Hom.: 2961 AF XY: 0.151 AC XY: 20498 AN XY: 135524

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.156 AC: 227437 AN: 1460582 Hom.: 17983 Cov.: 32 AF XY: 0.157 AC XY: 113837 AN XY: 726616

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.0956

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.159 AC: 24234 AN: 151998 Hom.: 1974 Cov.: 31 AF XY: 0.161 AC XY: 11922 AN XY: 74272

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.145

Alfa AF: 0.154 Hom.: 4236

Bravo AF: 0.154

TwinsUK AF: 0.148 AC: 547

ALSPAC AF: 0.157 AC: 604

ESP6500AA AF: 0.180 AC: 794

ESP6500EA AF: 0.152 AC: 1310

ExAC AF: 0.151 AC: 18359

Asia WGS AF: 0.137 AC: 478 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.4
DANN	Benign	0.064
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.7	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.044
MPC		0.22
ClinPred		0.0039	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.036
gMVP		0.49

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: rs7739323; hg19: chr6-83667045; COSMIC: COSV52753954;