chr7-157178682-T-C

Position:

• chr7-157178682-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_014671.3(UBE3C):​c.459-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,611,542 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (71 hom.)
• Consequence: UBE3C NM_014671.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003684
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.17

Genes affected

UBE3C (HGNC:16803): (ubiquitin protein ligase E3C) Enables ubiquitin protein ligase activity. Involved in protein polyubiquitination. Predicted to be located in nucleus. Predicted to be part of proteasome complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 7-157178682-T-C is Benign according to our data. Variant chr7-157178682-T-C is described in ClinVar as [Benign]. Clinvar id is 3043379.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0014 (214/152326) while in subpopulation SAS AF= 0.0257 (124/4826). AF 95% confidence interval is 0.022. There are 4 homozygotes in gnomad4. There are 127 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE3C	NM_014671.3	c.459-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000348165.10	NP_055486.2
UBE3C	XM_005249564.5	c.384-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_005249621.1
UBE3C	XM_047421072.1	c.396-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_047277028.1
UBE3C	XM_047421073.1	c.459-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10	c.459-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014671.3	ENSP00000309198	P1
UBE3C	ENST00000389103.4	c.330-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000373755

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152208 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00392 AC: 982 AN: 250396 Hom.: 22 AF XY: 0.00517 AC XY: 700 AN XY: 135362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00161

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0257

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00233 AC: 3399 AN: 1459216 Hom.: 71 Cov.: 30 AF XY: 0.00310 AC XY: 2248 AN XY: 725590

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00177

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000703

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00140 AC: 214 AN: 152326 Hom.: 4 Cov.: 32 AF XY: 0.00171 AC XY: 127 AN XY: 74482

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000955

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.000793

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.00159

EpiControl AF: 0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

UBE3C-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 04, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00037
dbscSNV1_RF	Benign	0.054
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: rs199836750; hg19: chr7-156971376;