Variant rs782375893 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The ENST00000262854.11(HUWE1):c.9468_9470del(p.Gly3157del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000174 in 1,208,160 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000016 ( 0 hom. 6 hem. )

Consequence

HUWE1
ENST00000262854.11 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.15

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 Likely_benign. Variant got -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in ENST00000262854.11. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant X-53550683-ACCC-A is Benign according to our data. Variant chrX-53550683-ACCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 211171.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUWE1	NM_031407.7 linkuse as main transcript	c.9468_9470del	p.Gly3157del	inframe_deletion	66/84	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.9468_9470del	p.Gly3157del	inframe_deletion	66/84	1	NM_031407.7	ENSP00000262854	P2	Q7Z6Z7-1
HUWE1	ENST00000342160.7 linkuse as main transcript	c.9468_9470del	p.Gly3157del	inframe_deletion	65/83	5		ENSP00000340648	P2	Q7Z6Z7-1
HUWE1	ENST00000612484.4 linkuse as main transcript	c.9441_9443del	p.Gly3148del	inframe_deletion	63/81	5		ENSP00000479451	A2	Q7Z6Z7-3
HUWE1	ENST00000704099.1 linkuse as main transcript	c.9465_9467del	p.Gly3156del	inframe_deletion	65/83			ENSP00000515693

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

110895

Hom.:

Cov.:

AF XY:

0.0000603

AC XY:

AN XY:

33161

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000959

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:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183091

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67763

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000612

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1097265

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

362653

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000178

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000271

AC:

AN:

110895

Hom.:

Cov.:

AF XY:

0.0000603

AC XY:

AN XY:

33161

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000959

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000907

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 18, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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