Variant chr10-67932719-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015601.4(HERC4):c.2716G>A(p.Asp906Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,600,054 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 16 hom. )

Consequence

HERC4
NM_015601.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

HERC4 (HGNC:24521): (HECT and RLD domain containing E3 ubiquitin protein ligase 4) HERC4 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]

HERC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009596795).

BP6

Variant 10-67932719-C-T is Benign according to our data. Variant chr10-67932719-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640521.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 350 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC4	NM_015601.4 linkuse as main transcript	c.2716G>A	p.Asp906Asn	missense_variant	23/25	ENST00000373700.9	NP_056416.2	Q5GLZ8-2A0A024QZN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC4	ENST00000373700.9 linkuse as main transcript	c.2716G>A	p.Asp906Asn	missense_variant	23/25	1	NM_015601.4	ENSP00000362804.4		Q5GLZ8-2

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

349

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00288

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00236

AC:

557

AN:

235546

Hom.:

AF XY:

0.00250

AC XY:

318

AN XY:

127250

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.00241

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00308

Gnomad FIN exome

AF:

0.00448

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00241

GnomAD4 exome

AF:

0.00200

AC:

2902

AN:

1447808

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1522

AN XY:

719928

show subpopulations

Gnomad4 AFR exome

AF:

0.000865

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00179

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00307

Gnomad4 FIN exome

AF:

0.00360

Gnomad4 NFE exome

AF:

0.00191

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00230

AC:

350

AN:

152246

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.00290

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00247

Hom.:

Bravo

AF:

0.00213

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00232

AC:

282

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00374

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

Sep 01, 2023

HERC4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;.;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.0096

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

.;.;N;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.50

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.51

T;T;T;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.0020

B;B;B;B

Vest4

0.26

MVP

0.36

MPC

0.76

ClinPred

0.0089

GERP RS

5.2

Varity_R

0.059

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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