Variant chr14-31113320-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015382.4(HECTD1):c.6021A>G(p.Leu2007Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,613,126 control chromosomes in the GnomAD database, including 152,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19868 hom., cov: 32)

Exomes 𝑓: 0.42 ( 133095 hom. )

Consequence

HECTD1
NM_015382.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.826

Variant links:

Genes affected

HECTD1 (HGNC:20157): (HECT domain E3 ubiquitin protein ligase 1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in anatomical structure development; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and protein K63-linked ubiquitination. Predicted to act upstream of or within several processes, including animal organ development; negative regulation of protein localization to plasma membrane; and protein autoubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

HECTD1 links:

AP4S1 (HGNC:575): (adaptor related protein complex 4 subunit sigma 1) This gene encodes a member of the adaptor complexes small subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is the small subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Mutations in this gene are associated with spastic quadriplegic cerebral palsy-6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Dec 2011]

AP4S1 links:

HECTD1 (HGNC:):

HECTD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 14-31113320-T-C is Benign according to our data. Variant chr14-31113320-T-C is described in ClinVar as [Benign]. Clinvar id is 1338873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.826 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HECTD1	NM_015382.4 linkuse as main transcript	c.6021A>G	p.Leu2007Leu	synonymous_variant	33/43	ENST00000399332.6	NP_056197.3	Q9ULT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HECTD1	ENST00000399332.6 linkuse as main transcript	c.6021A>G	p.Leu2007Leu	synonymous_variant	33/43	5	NM_015382.4	ENSP00000382269.1		Q9ULT8

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75241

AN:

151956

Hom.:

19822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.686

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.418

Gnomad OTH

AF:

0.472

GnomAD3 exomes

AF:

0.450

AC:

112204

AN:

249416

Hom.:

25938

AF XY:

0.447

AC XY:

60472

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.689

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.423

AC:

618051

AN:

1461052

Hom.:

133095

Cov.:

AF XY:

0.425

AC XY:

308584

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.695

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.356

Gnomad4 EAS exome

AF:

0.363

Gnomad4 SAS exome

AF:

0.505

Gnomad4 FIN exome

AF:

0.433

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.426

GnomAD4 genome

AF:

0.495

AC:

75351

AN:

152074

Hom.:

19868

Cov.:

AF XY:

0.492

AC XY:

36529

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.687

Gnomad4 AMR

AF:

0.451

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.376

Gnomad4 SAS

AF:

0.524

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.418

Gnomad4 OTH

AF:

0.469

Alfa

AF:

0.427

Hom.:

18728

Bravo

AF:

0.503

Asia WGS

AF:

0.456

AC:

1585

AN:

3474

EpiCase

AF:

0.405

EpiControl

AF:

0.400

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	Jan 27, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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