Variant 17-75831355-CG-CGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_199242.3(UNC13D):c.2448-8dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,609,058 control chromosomes in the GnomAD database, including 22,339 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 8033 hom., cov: 28)

Exomes 𝑓: 0.099 ( 14306 hom. )

Consequence

UNC13D
NM_199242.3 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.316

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 17-75831355-C-CG is Benign according to our data. Variant chr17-75831355-C-CG is described in ClinVar as [Benign]. Clinvar id is 263226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 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.2448-8dupC		splice_region_variant, 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.2448-8dupC		splice_region_variant, intron_variant		1	NM_199242.3	ENSP00000207549.3		Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35625

AN:

151958

Hom.:

8007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.0549

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.0731

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.147

AC:

35586

AN:

242408

Hom.:

5036

AF XY:

0.141

AC XY:

18694

AN XY:

132314

show subpopulations

Gnomad AFR exome

AF:

0.605

Gnomad AMR exome

AF:

0.0971

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.333

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.0530

Gnomad NFE exome

AF:

0.0747

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.0992

AC:

144541

AN:

1456982

Hom.:

14306

Cov.:

AF XY:

0.101

AC XY:

72890

AN XY:

724952

show subpopulations

Gnomad4 AFR exome

AF:

0.608

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.0555

Gnomad4 NFE exome

AF:

0.0671

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.235

AC:

35692

AN:

152076

Hom.:

8033

Cov.:

AF XY:

0.232

AC XY:

17240

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.587

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.0549

Gnomad4 NFE

AF:

0.0731

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.161

Hom.:

742

Bravo

AF:

0.258

EpiCase

AF:

0.0856

EpiControl

AF:

0.0853

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	PreventionGenetics, part of Exact Sciences	-	- -
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 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Familial hemophagocytic lymphohistiocytosis 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Familial hemophagocytic lymphohistiocytosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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