12-112167363-T-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The NM_001388303.1(HECTD4):c.12488A>G(p.Gln4163Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0017 in 1,613,806 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 4 hom. )
Consequence
HECTD4
NM_001388303.1 missense
NM_001388303.1 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 3.81
Genes affected
HECTD4 (HGNC:26611): (HECT domain E3 ubiquitin protein ligase 4) Predicted to enable ubiquitin-protein transferase activity. Involved in glucose homeostasis and glucose metabolic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, HECTD4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009295464).
BP6
?
Variant 12-112167363-T-C is Benign according to our data. Variant chr12-112167363-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3048931.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HECTD4 | NM_001388303.1 | c.12488A>G | p.Gln4163Arg | missense_variant | 72/76 | ENST00000682272.1 | |
HECTD4 | NM_001109662.4 | c.12518A>G | p.Gln4173Arg | missense_variant | 72/76 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HECTD4 | ENST00000682272.1 | c.12488A>G | p.Gln4163Arg | missense_variant | 72/76 | NM_001388303.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00123 AC: 188AN: 152256Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00134 AC: 333AN: 249012Hom.: 2 AF XY: 0.00141 AC XY: 191AN XY: 135080
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GnomAD4 exome AF: 0.00175 AC: 2558AN: 1461432Hom.: 4 Cov.: 31 AF XY: 0.00177 AC XY: 1284AN XY: 726976
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GnomAD4 genome ? AF: 0.00123 AC: 188AN: 152374Hom.: 0 Cov.: 33 AF XY: 0.00117 AC XY: 87AN XY: 74514
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HECTD4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 01, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
REVEL
Benign
Sift4G
Benign
T;T
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at