Variant rs8067076 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.570-60T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,603,944 control chromosomes in the GnomAD database, including 109,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 20296 hom., cov: 28)

Exomes 𝑓: 0.34 ( 89615 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.408

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:

UNC13D (HGNC:):

UNC13D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 17-75841061-A-C is Benign according to our data. Variant chr17-75841061-A-C is described in ClinVar as [Benign]. Clinvar id is 1249408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 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.570-60T>G		intron_variant		ENST00000207549.9	NP_954712.1	Q70J99-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13D	ENST00000207549.9 linkuse as main transcript	c.570-60T>G		intron_variant		1	NM_199242.3	ENSP00000207549.3		Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70062

AN:

150622

Hom.:

20246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.340

AC:

493881

AN:

1453214

Hom.:

89615

Cov.:

AF XY:

0.340

AC XY:

245972

AN XY:

723416

show subpopulations

Gnomad4 AFR exome

AF:

0.847

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.411

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.465

AC:

70162

AN:

150730

Hom.:

20296

Cov.:

AF XY:

0.457

AC XY:

33591

AN XY:

73510

show subpopulations

Gnomad4 AFR

AF:

0.827

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.422

Gnomad4 EAS

AF:

0.417

Gnomad4 SAS

AF:

0.351

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.460

Alfa

AF:

0.349

Hom.:

9955

Bravo

AF:

0.492

Asia WGS

AF:

0.409

AC:

1422

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.1

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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