rs79450945

Variant names:

• chr1-45003724-C-A
• NM_024602.6:c.2446G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-45003724-C-A
• chr1-45003724-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024602.6(HECTD3):​c.2446G>T​(p.Ala816Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A816T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HECTD3 NM_024602.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

HECTD3 (HGNC:26117): (HECT domain E3 ubiquitin protein ligase 3) The protein encoded by this gene transfers ubiquitin from an E2 ubiquitin-conjugating enzyme to targeted substrates, leading to the degradation of those substrates. The encoded protein has been shown to transfer ubiquitin to TRIOBP to facilitate cell cycle progression, and to STX8. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16823769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HECTD3	NM_024602.6	c.2446G>T	p.Ala816Ser	missense_variant	Exon 20 of 21	ENST00000372172.5	NP_078878.3
HECTD3	XM_047430487.1	c.1594G>T	p.Ala532Ser	missense_variant	Exon 18 of 19		XP_047286443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECTD3	ENST00000372172.5	c.2446G>T	p.Ala816Ser	missense_variant	Exon 20 of 21	5	NM_024602.6	ENSP00000361245.4
HECTD3	ENST00000486132.5	n.1293G>T		non_coding_transcript_exon_variant	Exon 5 of 6	1
HECTD3	ENST00000372168.7	c.1276G>T	p.Ala426Ser	missense_variant	Exon 12 of 13	2		ENSP00000361241.3
HECTD3	ENST00000486296.5	n.*131G>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.19	.;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.063
Sift	Benign	0.47	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.044	B;B
Vest4		0.23
MutPred		0.40		.;Gain of phosphorylation at A816 (P = 0.0318);
MVP		0.57
MPC		0.41
ClinPred		0.54	D
GERP RS		5.7
Varity_R		0.034
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45469396;