chr7-157238575-A-G

Variant names:

• chr7-157238575-A-G
• rs1182398
• NM_014671.3:c.2481+7248A>G

Variant summary

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

The NM_014671.3(UBE3C):​c.2481+7248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,226 control chromosomes in the GnomAD database, including 69,343 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 0.95 (69343 hom., cov: 30)
• Consequence: UBE3C NM_014671.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE3C	NM_014671.3	c.2481+7248A>G		intron_variant	Intron 18 of 22	ENST00000348165.10	NP_055486.2
UBE3C	XM_047421072.1	c.2418+7248A>G		intron_variant	Intron 18 of 22		XP_047277028.1
UBE3C	XM_005249564.5	c.2406+7248A>G		intron_variant	Intron 17 of 21		XP_005249621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10	c.2481+7248A>G		intron_variant	Intron 18 of 22	1	NM_014671.3	ENSP00000309198.8
UBE3C	ENST00000470408.5	n.3065+7248A>G		intron_variant	Intron 3 of 7	2
UBE3C	ENST00000494532.1	n.286+7248A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145126 AN: 152108 Hom.: 69282 Cov.: 30

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.954 AC: 145246 AN: 152226 Hom.: 69343 Cov.: 30 AF XY: 0.955 AC XY: 71084 AN XY: 74432

African (AFR) AF: 0.988 AC: 41022 AN: 41528

American (AMR) AF: 0.953 AC: 14576 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3294 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5155 AN: 5182

South Asian (SAS) AF: 0.970 AC: 4679 AN: 4826

European-Finnish (FIN) AF: 0.955 AC: 10118 AN: 10598

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63199 AN: 68016

Other (OTH) AF: 0.960 AC: 2026 AN: 2110

Alfa AF: 0.941 Hom.: 47394

Bravo AF: 0.955

Asia WGS AF: 0.981 AC: 3410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1182398; hg19: chr7-157031269;