Variant 6-104744232-TAAC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020771.4(HACE1):c.2443-5_2443-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,575,176 control chromosomes in the GnomAD database, including 24,603 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4917 hom., cov: 26)

Exomes 𝑓: 0.15 ( 19686 hom. )

Consequence

HACE1
NM_020771.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.25

Variant links:

Genes affected

HACE1 (HGNC:21033): (HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1) This gene encodes a HECT domain and ankyrin repeat-containing ubiquitin ligase. The encoded protein is involved in specific tagging of target proteins, leading to their subcellular localization or proteasomal degradation. The protein is a potential tumor suppressor and is involved in the pathophysiology of several tumors, including Wilm's tumor. [provided by RefSeq, Mar 2016]

HACE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 6-104744232-TAAC-T is Benign according to our data. Variant chr6-104744232-TAAC-T is described in ClinVar as [Benign]. Clinvar id is 1599999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACE1	NM_020771.4 linkuse as main transcript	c.2443-5_2443-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262903.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACE1	ENST00000262903.9 linkuse as main transcript	c.2443-5_2443-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020771.4	P1	Q8IYU2-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34021

AN:

151752

Hom.:

4900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.164

AC:

41071

AN:

250952

Hom.:

4173

AF XY:

0.160

AC XY:

21687

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.421

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.00495

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.155

AC:

220054

AN:

1423308

Hom.:

19686

AF XY:

0.155

AC XY:

110098

AN XY:

710576

show subpopulations

Gnomad4 AFR exome

AF:

0.418

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.00563

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.224

AC:

34077

AN:

151868

Hom.:

4917

Cov.:

AF XY:

0.221

AC XY:

16372

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.00676

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.190

Hom.:

617

Bravo

AF:

0.240

Asia WGS

AF:

0.0930

AC:

321

AN:

3470

EpiCase

AF:

0.164

EpiControl

AF:

0.166

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Spastic paraplegia-severe developmental delay-epilepsy syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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