Variant rs3744024 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199242.3(UNC13D):c.1728-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,608,438 control chromosomes in the GnomAD database, including 20,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 7615 hom., cov: 33)

Exomes 𝑓: 0.093 ( 13037 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.114

Variant links:

Genes affected

UNC13D (HGNC:23147): (unc-13 homolog D) This gene encodes a protein that is a member of the UNC13 family, containing similar domain structure as other family members but lacking an N-terminal phorbol ester-binding C1 domain present in other Munc13 proteins. The protein appears to play a role in vesicle maturation during exocytosis and is involved in regulation of cytolytic granules secretion. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis type 3, a genetically heterogeneous, rare autosomal recessive disorder. [provided by RefSeq, Jul 2008]

UNC13D links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 17-75835577-A-G is Benign according to our data. Variant chr17-75835577-A-G is described in ClinVar as [Benign]. Clinvar id is 263217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13D	NM_199242.3 linkuse as main transcript	c.1728-48T>C		intron_variant		ENST00000207549.9	NP_954712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13D	ENST00000207549.9 linkuse as main transcript	c.1728-48T>C		intron_variant		1	NM_199242.3	ENSP00000207549	P1	Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34519

AN:

152028

Hom.:

7596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.0529

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.0683

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.139

AC:

33088

AN:

238450

Hom.:

4532

AF XY:

0.132

AC XY:

17168

AN XY:

129878

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.0925

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.337

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.0508

Gnomad NFE exome

AF:

0.0693

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.0932

AC:

135673

AN:

1456292

Hom.:

13037

Cov.:

AF XY:

0.0941

AC XY:

68176

AN XY:

724146

show subpopulations

Gnomad4 AFR exome

AF:

0.594

Gnomad4 AMR exome

AF:

0.0974

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.151

Gnomad4 FIN exome

AF:

0.0533

Gnomad4 NFE exome

AF:

0.0625

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.227

AC:

34580

AN:

152146

Hom.:

7615

Cov.:

AF XY:

0.225

AC XY:

16739

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.0529

Gnomad4 NFE

AF:

0.0683

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.152

Hom.:

711

Bravo

AF:

0.250

Asia WGS

AF:

0.231

AC:

804

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.7

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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