chr12-112167391-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001388303.1(HECTD4):c.12460G>A(p.Glu4154Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000787 in 1,613,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000081 ( 0 hom. )
Consequence
HECTD4
NM_001388303.1 missense
NM_001388303.1 missense
Scores
1
6
7
Clinical Significance
Conservation
PhyloP100: 4.57
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, HECTD4
BP4
Computational evidence support a benign effect (MetaRNN=0.23649111).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HECTD4 | NM_001388303.1 | c.12460G>A | p.Glu4154Lys | missense_variant | 72/76 | ENST00000682272.1 | |
HECTD4 | NM_001109662.4 | c.12490G>A | p.Glu4164Lys | missense_variant | 72/76 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HECTD4 | ENST00000682272.1 | c.12460G>A | p.Glu4154Lys | missense_variant | 72/76 | NM_001388303.1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249088Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135128
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GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461468Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56AN XY: 727032
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74368
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 09, 2022 | The c.11944G>A (p.E3982K) alteration is located in exon 71 (coding exon 70) of the HECTD4 gene. This alteration results from a G to A substitution at nucleotide position 11944, causing the glutamic acid (E) at amino acid position 3982 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
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