Variant rs3744010 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.117+59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,589,986 control chromosomes in the GnomAD database, including 53,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8244 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44788 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.50

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=-0.81).

BP6

Variant 17-75844162-G-A is Benign according to our data. Variant chr17-75844162-G-A is described in ClinVar as [Benign]. Clinvar id is 1166947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75844162-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 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.117+59C>T		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.117+59C>T		intron_variant		1	NM_199242.3	ENSP00000207549	P1	Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46186

AN:

151932

Hom.:

8216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.303

GnomAD4 exome

AF:

0.243

AC:

349789

AN:

1437936

Hom.:

44788

Cov.:

AF XY:

0.242

AC XY:

173596

AN XY:

716068

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.304

AC:

46264

AN:

152050

Hom.:

8244

Cov.:

AF XY:

0.296

AC XY:

21978

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.491

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.273

Hom.:

984

Bravo

AF:

0.319

Asia WGS

AF:

0.215

AC:

745

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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 39% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

Familial hemophagocytic lymphohistiocytosis 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.51

DANN

Benign

0.73

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