7-157181598-A-T

Position:

• chr7-157181598-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014671.3(UBE3C):​c.697A>T​(p.Ile233Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBE3C NM_014671.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.810

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047017753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE3C	NM_014671.3	c.697A>T	p.Ile233Leu	missense_variant	7/23	ENST00000348165.10	NP_055486.2
UBE3C	XM_047421072.1	c.634A>T	p.Ile212Leu	missense_variant	7/23		XP_047277028.1
UBE3C	XM_005249564.5	c.622A>T	p.Ile208Leu	missense_variant	6/22		XP_005249621.1
UBE3C	XM_047421073.1	c.697A>T	p.Ile233Leu	missense_variant	7/16		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10	c.697A>T	p.Ile233Leu	missense_variant	7/23	1	NM_014671.3	ENSP00000309198.8
UBE3C	ENST00000389103.4	c.568A>T	p.Ile190Leu	missense_variant	5/9	5		ENSP00000373755.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.697A>T (p.I233L) alteration is located in exon 7 (coding exon 7) of the UBE3C gene. This alteration results from a A to T substitution at nucleotide position 697, causing the isoleucine (I) at amino acid position 233 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T;T;.
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.050	N;.;N
REVEL	Benign	0.025
Sift	Benign	1.0	T;.;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.22
MutPred		0.40		Loss of catalytic residue at L238 (P = 0.0515);.;.;
MVP		0.12
MPC		0.20
ClinPred		0.15	T
GERP RS		2.8
Varity_R		0.049
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-156974292;