Variant chr4-88652084-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_014606.3(HERC3):c.459G>A(p.Ala153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,605,826 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

HERC3
NM_014606.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.618

Variant links:

Genes affected

HERC3 (HGNC:4876): (HECT and RLD domain containing E3 ubiquitin protein ligase 3) This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

HERC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 4-88652084-G-A is Benign according to our data. Variant chr4-88652084-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654943.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.618 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERC3	NM_014606.3 linkuse as main transcript	c.459G>A	p.Ala153=	synonymous_variant	5/26	ENST00000402738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HERC3	ENST00000402738.6 linkuse as main transcript	c.459G>A	p.Ala153=	synonymous_variant	5/26	1	NM_014606.3	P1	Q15034-1
HERC3	ENST00000264345.7 linkuse as main transcript	c.459G>A	p.Ala153=	synonymous_variant	3/24	1		P1	Q15034-1
HERC3	ENST00000407637.5 linkuse as main transcript	c.459G>A	p.Ala153=	synonymous_variant	5/9	1			Q15034-2
HERC3	ENST00000452979.5 linkuse as main transcript	c.459G>A	p.Ala153=	synonymous_variant	5/6	3

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00201

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00121

AC:

303

AN:

251290

Hom.:

AF XY:

0.00109

AC XY:

148

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00237

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00160

AC:

2325

AN:

1453600

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1101

AN XY:

723682

show subpopulations

Gnomad4 AFR exome

AF:

0.000270

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.000955

Gnomad4 NFE exome

AF:

0.00199

Gnomad4 OTH exome

AF:

0.000915

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152226

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00201

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00104

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

HERC3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over