12-112163079-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001388303.1(HECTD4):c.13083G>A(p.Pro4361=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 1,613,118 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (57 hom.)
• Consequence: HECTD4 NM_001388303.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -9.36

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 12-112163079-C-T is Benign according to our data. Variant chr12-112163079-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.36 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECTD4	NM_001388303.1	c.13083G>A	p.Pro4361=	synonymous_variant	75/76	ENST00000682272.1
HECTD4	NM_001109662.4	c.13113G>A	p.Pro4371=	synonymous_variant	75/76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECTD4	ENST00000682272.1	c.13083G>A	p.Pro4361=	synonymous_variant	75/76		NM_001388303.1	P4

Frequencies

GnomAD3 genomes AF: 0.00531 AC: 806 AN: 151776 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00148

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00623 AC: 1548 AN: 248352 Hom.: 9 AF XY: 0.00665 AC XY: 896 AN XY: 134718

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00170

Gnomad EAS exome AF: 0.000723

Gnomad SAS exome AF: 0.00478

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.00857

Gnomad OTH exome AF: 0.00565

GnomAD4 exome AF: 0.00701 AC: 10242 AN: 1461224 Hom.: 57 Cov.: 32 AF XY: 0.00706 AC XY: 5130 AN XY: 726890

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.00413

Gnomad4 FIN exome AF: 0.0152

Gnomad4 NFE exome AF: 0.00774

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome AF: 0.00530 AC: 805 AN: 151894 Hom.: 4 Cov.: 32 AF XY: 0.00610 AC XY: 453 AN XY: 74240

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000778

Gnomad4 SAS AF: 0.00561

Gnomad4 FIN AF: 0.0177

Gnomad4 NFE AF: 0.00717

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00601 Hom.: 4

Bravo AF: 0.00385

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00731

EpiControl AF: 0.00730

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	HECTD4: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.58
Dann	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs183882784; hg19: chr12-112600883;