dbSNP rs766237206: UBE3C:p.Tyr105Asn (chr7-157170421-T-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014671.3(UBE3C):c.313T>A(p.Tyr105Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,409,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y105H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

UBE3C
NM_014671.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.84

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE3C	NM_014671.3 link	c.313T>A	p.Tyr105Asn	missense_variant	Exon 4 of 23	ENST00000348165.10	NP_055486.2	Q15386-1
UBE3C	XM_047421072.1 link	c.250T>A	p.Tyr84Asn	missense_variant	Exon 4 of 23		XP_047277028.1
UBE3C	XM_005249564.5 link	c.238T>A	p.Tyr80Asn	missense_variant	Exon 3 of 22		XP_005249621.1
UBE3C	XM_047421073.1 link	c.313T>A	p.Tyr105Asn	missense_variant	Exon 4 of 16		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBE3C	ENST00000348165.10 link	c.313T>A	p.Tyr105Asn	missense_variant	Exon 4 of 23	1	NM_014671.3	ENSP00000309198.8	Q15386-1
UBE3C	ENST00000389103.4 link	c.184T>A	p.Tyr62Asn	missense_variant	Exon 2 of 9	5		ENSP00000373755.4	Q15386-3
UBE3C	ENST00000430750.1 link	n.*248T>A		non_coding_transcript_exon_variant	Exon 5 of 5	4		ENSP00000397432.1	H7C0Y1
UBE3C	ENST00000430750.1 link	n.*248T>A		3_prime_UTR_variant	Exon 5 of 5	4		ENSP00000397432.1	H7C0Y1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000477

AC:

AN:

209644

Hom.:

AF XY:

0.00

AC XY:

AN XY:

114216

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000422

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1409414

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000299

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

D;.;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D;.

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.8

M;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.6

D;.;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0030

D;.;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.96

MutPred

0.78

Loss of stability (P = 0.0378);.;.;

MVP

0.36

MPC

1.0

ClinPred

0.98

GERP RS

4.8

Varity_R

0.75

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over