Variant 15-90931401-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001286451.2(HDDC3):c.414G>A(p.Trp138*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00512 in 1,582,088 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 21 hom. )

Consequence

HDDC3
NM_001286451.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.84

Variant links:

Genes affected

HDDC3 (HGNC:30522): (HD domain containing 3) Predicted to enable guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity. [provided by Alliance of Genome Resources, Apr 2022]

HDDC3 links:

UNC45A (HGNC:30594): (unc-45 myosin chaperone A) This gene encodes a regulatory component of the progesterone receptor/heat shock protein 90 chaperoning complex, which functions in the assembly and folding of the progesterone receptor. The encoded protein is thought to be essential for normal cell proliferation, and for the accumulation of myosin during development of muscle cells. [provided by RefSeq, Sep 2018]

UNC45A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 15-90931401-C-T is Benign according to our data. Variant chr15-90931401-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645716.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDDC3	NM_001286451.2 link	c.414G>A	p.Trp138*	stop_gained	4/4	ENST00000394272.8	NP_001273380.1	Q8N4P3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDDC3	ENST00000394272.8 link	c.414G>A	p.Trp138*	stop_gained	4/4	2	NM_001286451.2	ENSP00000377814.4		Q8N4P3-1

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

513

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00610

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00287

AC:

585

AN:

203856

Hom.:

AF XY:

0.00287

AC XY:

314

AN XY:

109504

show subpopulations

Gnomad AFR exome

AF:

0.000700

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.000213

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000299

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00556

Gnomad OTH exome

AF:

0.00241

GnomAD4 exome

AF:

0.00530

AC:

7582

AN:

1429816

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

3623

AN XY:

708756

show subpopulations

Gnomad4 AFR exome

AF:

0.000803

Gnomad4 AMR exome

AF:

0.00169

Gnomad4 ASJ exome

AF:

0.000467

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000350

Gnomad4 FIN exome

AF:

0.00212

Gnomad4 NFE exome

AF:

0.00647

Gnomad4 OTH exome

AF:

0.00415

GnomAD4 genome

AF:

0.00337

AC:

513

AN:

152272

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00610

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00494

Hom.:

Bravo

AF:

0.00328

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00597

AC:

ExAC

AF:

0.00266

AC:

320

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

HDDC3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

Vest4

0.20

GERP RS

4.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over