rs7739323

Variant names:

• chr6-82957326-C-T
• rs7739323
• NM_198920.3:c.1135G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198920.3. 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
	UBE3D	NM_198920.3	MANE Select	c.1135G>A	p.Val379Met	missense	Exon 9 of 10	NP_944602.1	Q7Z6J8
	UBE3D	NM_001304437.2		c.1039G>A	p.Val347Met	missense	Exon 9 of 10	NP_001291366.1
	UBE3D	NM_001350602.2		c.1039G>A	p.Val347Met	missense	Exon 10 of 11	NP_001337531.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3D	ENST00000369747.8	TSL:1 MANE Select	c.1135G>A	p.Val379Met	missense	Exon 9 of 10	ENSP00000358762.3	Q7Z6J8
	UBE3D	ENST00000237186.10	TSL:1	n.*986G>A		non_coding_transcript_exon	Exon 9 of 10	ENSP00000237186.6	J3KMY4
	UBE3D	ENST00000509102.5	TSL:1	n.*254G>A		non_coding_transcript_exon	Exon 9 of 10	ENSP00000427101.1	D6RD24

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

GnomAD2 exomes AF: 0.150 AC: 37515 AN: 250862 AF XY: 0.151

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 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

African (AFR) AF: 0.172 AC: 5755 AN: 33428

American (AMR) AF: 0.118 AC: 5271 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 2497 AN: 26126

East Asian (EAS) AF: 0.113 AC: 4467 AN: 39684

South Asian (SAS) AF: 0.172 AC: 14826 AN: 86132

European-Finnish (FIN) AF: 0.160 AC: 8562 AN: 53418

Middle Eastern (MID) AF: 0.137 AC: 789 AN: 5766

European-Non Finnish (NFE) AF: 0.159 AC: 176202 AN: 1111016

Other (OTH) AF: 0.150 AC: 9068 AN: 60358

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

African (AFR) AF: 0.173 AC: 7170 AN: 41442

American (AMR) AF: 0.149 AC: 2270 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3470

East Asian (EAS) AF: 0.131 AC: 674 AN: 5144

South Asian (SAS) AF: 0.173 AC: 834 AN: 4814

European-Finnish (FIN) AF: 0.162 AC: 1710 AN: 10554

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10888 AN: 67992

Other (OTH) AF: 0.145 AC: 305 AN: 2104

Alfa AF: 0.156 Hom.: 8699

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 v4.9

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
PhyloP100		1.6
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
Mutation Taster		=100/0	polymorphism (auto)

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