1-45006708-A-G

Position:

• chr1-45006708-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024602.6(HECTD3):​c.1709T>C​(p.Val570Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HECTD3 NM_024602.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28702307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECTD3	NM_024602.6	c.1709T>C	p.Val570Ala	missense_variant	13/21	ENST00000372172.5
HECTD3	XM_047430487.1	c.857T>C	p.Val286Ala	missense_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECTD3	ENST00000372172.5	c.1709T>C	p.Val570Ala	missense_variant	13/21	5	NM_024602.6	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2023

The c.1709T>C (p.V570A) alteration is located in exon 13 (coding exon 13) of the HECTD3 gene. This alteration results from a T to C substitution at nucleotide position 1709, causing the valine (V) at amino acid position 570 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.45	T
MutationTaster	Benign	0.85	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		0.40	B;B
Vest4		0.32
MutPred		0.60		.;Loss of sheet (P = 0.0104);
MVP		0.59
MPC		0.97
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.35

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: chr1-45472380;