1-45004105-A-C

Variant names:

• chr1-45004105-A-C
• rs201781168
• NM_024602.6:c.2302T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024602.6(HECTD3):​c.2302T>G​(p.Ser768Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000091 (0 hom.)
• Consequence: HECTD3 NM_024602.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.95
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018582731).

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.2302T>G	p.Ser768Ala	missense	Exon 18 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.2302T>G	p.Ser768Ala	missense	Exon 18 of 21	ENSP00000361245.4	Q5T447-1
	HECTD3	ENST00000486132.5	TSL:1	n.1149T>G		non_coding_transcript_exon	Exon 3 of 6
	HECTD3	ENST00000875142.1		c.2443T>G	p.Ser815Ala	missense	Exon 18 of 21	ENSP00000545201.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000406 AC: 10 AN: 246524 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000813

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000910 AC: 133 AN: 1461794 Hom.: 0 Cov.: 33 AF XY: 0.0000866 AC XY: 63 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1112010

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000961 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.66
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		2.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.049
Sift	Benign	0.73	T
Sift4G	Benign	0.86	T
Polyphen		0.010	B
Vest4		0.22
MVP		0.39
MPC		0.38
ClinPred		0.016	T
GERP RS		4.0
Varity_R		0.037
gMVP		0.21
Mutation Taster		=97/3	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: rs201781168; hg19: chr1-45469777;