chr1-45003724-C-A

Variant names:

• chr1-45003724-C-A
• rs79450945
• NM_024602.6:c.2446G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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]

ENSG00000300507 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024602.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD3	NM_024602.6	MANE Select	c.2446G>T	p.Ala816Ser	missense	Exon 20 of 21	NP_078878.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD3	ENST00000372172.5	TSL:5 MANE Select	c.2446G>T	p.Ala816Ser	missense	Exon 20 of 21	ENSP00000361245.4	Q5T447-1
	HECTD3	ENST00000486132.5	TSL:1	n.1293G>T		non_coding_transcript_exon	Exon 5 of 6
	HECTD3	ENST00000875142.1		c.2587G>T	p.Ala863Ser	missense	Exon 20 of 21	ENSP00000545201.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.19	N
PhyloP100		2.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.063
Sift	Benign	0.47	T
Sift4G	Benign	0.66	T
Polyphen		0.044	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
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs79450945; hg19: chr1-45469396;