Variant 14-31107208-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015382.4(HECTD1):c.6664A>C(p.Arg2222Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,613,086 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

HECTD1
NM_015382.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.16

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-31107208-T-G is Benign according to our data. Variant chr14-31107208-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3387895.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.16 with no splicing effect.

BS2

High AC in GnomAd4 at 180 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HECTD1	NM_015382.4 linkuse as main transcript	c.6664A>C	p.Arg2222Arg	synonymous_variant	38/43	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.6664A>C	p.Arg2222Arg	synonymous_variant	38/43	5	NM_015382.4	ENSP00000382269.1		Q9ULT8

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

180

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00102

AC:

252

AN:

247070

Hom.:

AF XY:

0.000961

AC XY:

129

AN XY:

134248

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.000437

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00182

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.00179

AC:

2612

AN:

1460764

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1266

AN XY:

726492

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000560

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.00118

AC:

180

AN:

152322

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00155

Hom.:

Bravo

AF:

0.00113

EpiCase

AF:

0.00213

EpiControl

AF:

0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

HECTD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.7

DANN

Benign

0.83

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