chr7-157178682-T-C

Variant names:

• chr7-157178682-T-C
• rs199836750
• NM_014671.3:c.459-8T>C

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.0003684
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

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]

UBE3C Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with absent speech and movement and behavioral abnormalities

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014671.3. 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
	UBE3C	NM_014671.3	MANE Select	c.459-8T>C		splice_region intron	N/A	NP_055486.2	Q15386-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3C	ENST00000348165.10	TSL:1 MANE Select	c.459-8T>C		splice_region intron	N/A	ENSP00000309198.8	Q15386-1
	UBE3C	ENST00000945962.1		c.459-8T>C		splice_region intron	N/A	ENSP00000616021.1
	UBE3C	ENST00000945960.1		c.534-8T>C		splice_region intron	N/A	ENSP00000616019.1

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

GnomAD2 exomes AF: 0.00392 AC: 982 AN: 250396 AF XY: 0.00517

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 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

African (AFR) AF: 0.000150 AC: 5 AN: 33442

American (AMR) AF: 0.00114 AC: 51 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 46 AN: 25998

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39646

South Asian (SAS) AF: 0.0267 AC: 2294 AN: 86078

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53270

Middle Eastern (MID) AF: 0.00914 AC: 52 AN: 5692

European-Non Finnish (NFE) AF: 0.000703 AC: 780 AN: 1110188

Other (OTH) AF: 0.00280 AC: 169 AN: 60280

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

African (AFR) AF: 0.0000962 AC: 4 AN: 41570

American (AMR) AF: 0.000588 AC: 9 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0257 AC: 124 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000955 AC: 65 AN: 68036

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UBE3C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.67
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs199836750; hg19: chr7-156971376;