Variant X-53557457-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031407.7(HUWE1):c.8161-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,149,755 control chromosomes in the GnomAD database, including 3,121 homozygotes. There are 15,489 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 321 hom., 1625 hem., cov: 22)

Exomes 𝑓: 0.044 ( 2800 hom. 13864 hem. )

Consequence

HUWE1
NM_031407.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.761

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 -20 ACMG points.

BP4

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

BP6

Variant X-53557457-G-A is Benign according to our data. Variant chrX-53557457-G-A is described in ClinVar as [Benign]. Clinvar id is 1226397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUWE1	NM_031407.7 linkuse as main transcript	c.8161-30C>T		intron_variant		ENST00000262854.11	NP_113584.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
HUWE1	ENST00000262854.11 linkuse as main transcript	c.8161-30C>T	intron_variant	1	NM_031407.7	ENSP00000262854	P2	Q7Z6Z7-1
HUWE1	ENST00000342160.7 linkuse as main transcript	c.8161-30C>T	intron_variant	5		ENSP00000340648	P2	Q7Z6Z7-1
HUWE1	ENST00000612484.4 linkuse as main transcript	c.8134-30C>T	intron_variant	5		ENSP00000479451	A2	Q7Z6Z7-3
HUWE1	ENST00000704099.1 linkuse as main transcript	c.8158-30C>T	intron_variant			ENSP00000515693

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

5122

AN:

111891

Hom.:

320

Cov.:

AF XY:

0.0476

AC XY:

1623

AN XY:

34081

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.0356

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0231

Gnomad OTH

AF:

0.0584

GnomAD3 exomes

AF:

0.0900

AC:

16329

AN:

181518

Hom.:

1595

AF XY:

0.0736

AC XY:

4884

AN XY:

66318

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.0242

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.0269

Gnomad FIN exome

AF:

0.0394

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0610

GnomAD4 exome

AF:

0.0439

AC:

45588

AN:

1037811

Hom.:

2800

Cov.:

AF XY:

0.0446

AC XY:

13864

AN XY:

310725

show subpopulations

Gnomad4 AFR exome

AF:

0.00691

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.0232

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.0290

Gnomad4 FIN exome

AF:

0.0364

Gnomad4 NFE exome

AF:

0.0242

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0458

AC:

5122

AN:

111944

Hom.:

321

Cov.:

AF XY:

0.0476

AC XY:

1625

AN XY:

34144

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.0356

Gnomad4 NFE

AF:

0.0231

Gnomad4 OTH

AF:

0.0583

Alfa

AF:

0.0232

Hom.:

183

Bravo

AF:

0.0612

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.44

DANN

Benign

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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