Variant 14-31101195-G-A 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.7680C>T(p.Leu2560Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00633 in 1,614,190 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 88 hom. )

Consequence

HECTD1
NM_015382.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.09

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:

HECTD1 (HGNC:):

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:

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=-0.57).

BP6

Variant 14-31101195-G-A is Benign according to our data. Variant chr14-31101195-G-A is described in ClinVar as [Benign]. Clinvar id is 780155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0544 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.7680C>T	p.Leu2560Leu	synonymous_variant	42/43	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.7680C>T	p.Leu2560Leu	synonymous_variant	42/43	5	NM_015382.4	ENSP00000382269.1		Q9ULT8

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.0599

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00503

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00919

AC:

2293

AN:

249476

Hom.:

AF XY:

0.00932

AC XY:

1261

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00884

Gnomad EAS exome

AF:

0.0655

Gnomad SAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.00458

Gnomad OTH exome

AF:

0.00760

GnomAD4 exome

AF:

0.00631

AC:

9230

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

4711

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00945

Gnomad4 EAS exome

AF:

0.0555

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.00453

Gnomad4 OTH exome

AF:

0.00957

GnomAD4 genome

AF:

0.00652

AC:

993

AN:

152304

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

511

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00284

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.0599

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00503

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00561

Hom.:

Bravo

AF:

0.00686

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00616

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.9

DANN

Benign

0.76

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