Variant rs202214456 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_031407.7(HUWE1):c.8298A>G(p.Gln2766=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00079 in 1,208,523 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 290 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.00082 ( 0 hom. 279 hem. )

Consequence

HUWE1
NM_031407.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.744

Variant links:

Genes affected

HUWE1 (HGNC:30892): (HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1) This gene encodes a protein containing a C-terminal HECT (E6AP type E3 ubiquitin protein ligase) domain that functions as an E3 ubiquitin ligase. The encoded protein is required for the ubiquitination and subsequent degradation of the anti-apoptotic protein Mcl1 (myeloid cell leukemia sequence 1 (BCL2-related)). This protein also ubiquitinates the p53 tumor suppressor, core histones, and DNA polymerase beta. Mutations in this gene are associated with Turner type X-linked syndromic cognitive disability. [provided by RefSeq, Aug 2013]

HUWE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-53554829-T-C is Benign according to our data. Variant chrX-53554829-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 435477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.744 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUWE1	NM_031407.7 linkuse as main transcript	c.8298A>G	p.Gln2766=	synonymous_variant	61/84	ENST00000262854.11	NP_113584.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HUWE1	ENST00000262854.11 linkuse as main transcript	c.8298A>G	p.Gln2766=	synonymous_variant	61/84	1	NM_031407.7	ENSP00000262854	P2	Q7Z6Z7-1
HUWE1	ENST00000342160.7 linkuse as main transcript	c.8298A>G	p.Gln2766=	synonymous_variant	60/83	5		ENSP00000340648	P2	Q7Z6Z7-1
HUWE1	ENST00000612484.4 linkuse as main transcript	c.8271A>G	p.Gln2757=	synonymous_variant	58/81	5		ENSP00000479451	A2	Q7Z6Z7-3
HUWE1	ENST00000704099.1 linkuse as main transcript	c.8295A>G	p.Gln2765=	synonymous_variant	60/83			ENSP00000515693

Frequencies

GnomAD3 genomes

AF:

0.000503

AC:

AN:

111222

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

AN XY:

33428

show subpopulations

Gnomad AFR

AF:

0.000426

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000773

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000328

AC:

AN:

182922

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

67392

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.0000527

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000576

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000819

AC:

899

AN:

1097247

Hom.:

Cov.:

AF XY:

0.000769

AC XY:

279

AN XY:

362607

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.000199

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.0000663

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000717

GnomAD4 genome

AF:

0.000503

AC:

AN:

111276

Hom.:

Cov.:

AF XY:

0.000328

AC XY:

AN XY:

33492

show subpopulations

Gnomad4 AFR

AF:

0.000425

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000774

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000738

Hom.:

Bravo

AF:

0.000559

EpiCase

AF:

0.000437

EpiControl

AF:

0.000653

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	HUWE1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 15, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2020	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 22, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.25

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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