rs3802122

Variant names:

• chr7-157179604-T-A
• rs3802122
• NM_014671.3:c.616+757T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-157179604-T-A
• chr7-157179604-T-C

Variant summary

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

The NM_014671.3(UBE3C):​c.616+757T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,988 control chromosomes in the GnomAD database, including 10,371 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 0.34 (10371 hom., cov: 32)
• Consequence: UBE3C NM_014671.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE3C	NM_014671.3	c.616+757T>A		intron_variant	Intron 6 of 22	ENST00000348165.10	NP_055486.2
UBE3C	XM_047421072.1	c.553+757T>A		intron_variant	Intron 6 of 22		XP_047277028.1
UBE3C	XM_005249564.5	c.541+757T>A		intron_variant	Intron 5 of 21		XP_005249621.1
UBE3C	XM_047421073.1	c.616+757T>A		intron_variant	Intron 6 of 15		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10	c.616+757T>A		intron_variant	Intron 6 of 22	1	NM_014671.3	ENSP00000309198.8
UBE3C	ENST00000389103.4	c.487+757T>A		intron_variant	Intron 4 of 8	5		ENSP00000373755.4

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52385 AN: 151870 Hom.: 10361 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.345 AC: 52430 AN: 151988 Hom.: 10371 Cov.: 32 AF XY: 0.348 AC XY: 25829 AN XY: 74288

African (AFR) AF: 0.542 AC: 22447 AN: 41434

American (AMR) AF: 0.362 AC: 5529 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3466

East Asian (EAS) AF: 0.424 AC: 2188 AN: 5156

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4824

European-Finnish (FIN) AF: 0.249 AC: 2636 AN: 10566

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16415 AN: 67960

Other (OTH) AF: 0.333 AC: 703 AN: 2114

Alfa AF: 0.135 Hom.: 216

Bravo AF: 0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.84
PhyloP100		0.61
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: rs3802122; hg19: chr7-156972298;