4-88652084-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.618

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERC3	NM_014606.3	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	c.459G>A	p.Ala153=	synonymous_variant	5/26	1	NM_014606.3	P1
HERC3	ENST00000264345.7	c.459G>A	p.Ala153=	synonymous_variant	3/24	1		P1
HERC3	ENST00000407637.5	c.459G>A	p.Ala153=	synonymous_variant	5/9	1
HERC3	ENST00000452979.5	c.459G>A	p.Ala153=	synonymous_variant	5/6	3

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152110 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.00109 AC XY: 148 AN XY: 135810

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.: 5 Cov.: 27 AF XY: 0.00152 AC XY: 1101 AN XY: 723682

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.: 0 Cov.: 32 AF XY: 0.000914 AC XY: 68 AN XY: 74428

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.: 0

Bravo AF: 0.00104

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	13
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

Other links and lift over

dbSNP: rs143699412; hg19: chr4-89573235;