Variant 4-88463975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016323.4(HERC5):c.901G>A(p.Ala301Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00361 in 1,612,664 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.020 ( 93 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 96 hom. )

Consequence

HERC5
NM_016323.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

HERC5 (HGNC:24368): (HECT and RLD domain containing E3 ubiquitin protein ligase 5) This gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and perinuclear region and functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets. The protein also acts as a modulator of the antiviral immune response. The gene lies in a cluster of HERC family genes on chromosome 4. [provided by RefSeq, Aug 2021]

HERC5 links:

LOC102723458 (HGNC:):

LOC102723458 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013751119).

BP6

Variant 4-88463975-G-A is Benign according to our data. Variant chr4-88463975-G-A is described in ClinVar as [Benign]. Clinvar id is 780486.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HERC5	NM_016323.4 linkuse as main transcript	c.901G>A	p.Ala301Thr	missense_variant	6/23	ENST00000264350.8
HERC5	XM_011532022.3 linkuse as main transcript	c.901G>A	p.Ala301Thr	missense_variant	6/21
LOC102723458	XR_938972.3 linkuse as main transcript	n.19+3656C>T		intron_variant, non_coding_transcript_variant
LOC102723458	XR_938976.3 linkuse as main transcript	n.76+3656C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HERC5	ENST00000264350.8 linkuse as main transcript	c.901G>A	p.Ala301Thr	missense_variant	6/23	1	NM_016323.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2976

AN:

151750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00454

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0135

GnomAD3 exomes

AF:

0.00530

AC:

1330

AN:

250896

Hom.:

AF XY:

0.00375

AC XY:

508

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.0739

Gnomad AMR exome

AF:

0.00300

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00194

AC:

2835

AN:

1460796

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1203

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.0707

Gnomad4 AMR exome

AF:

0.00325

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.0197

AC:

2987

AN:

151868

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1443

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.0696

Gnomad4 AMR

AF:

0.00454

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00409

Hom.:

Bravo

AF:

0.0223

ESP6500AA

AF:

0.0699

AC:

308

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00661

AC:

802

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.87

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.38

Sift

Benign

0.21

Sift4G

Benign

0.28

Polyphen

0.97

Vest4

0.55

MVP

0.94

MPC

0.60

ClinPred

0.047

GERP RS

4.8

Varity_R

0.19

gMVP

0.51

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