Variant 17-75843133-G-C 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.261+26C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,610,152 control chromosomes in the GnomAD database, including 40,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3612 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36417 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.680

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:

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=-0.83).

BP6

Variant 17-75843133-G-C is Benign according to our data. Variant chr17-75843133-G-C is described in ClinVar as [Benign]. Clinvar id is 263229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13D	NM_199242.3 linkuse as main transcript	c.261+26C>G		intron_variant		ENST00000207549.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13D	ENST00000207549.9 linkuse as main transcript	c.261+26C>G		intron_variant		1	NM_199242.3	P1	Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32602

AN:

151922

Hom.:

3602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.0892

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.197

AC:

48293

AN:

245626

Hom.:

5035

AF XY:

0.199

AC XY:

26751

AN XY:

134162

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.0845

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.221

AC:

321663

AN:

1458112

Hom.:

36417

Cov.:

AF XY:

0.220

AC XY:

159521

AN XY:

725432

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.0910

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.215

AC:

32630

AN:

152040

Hom.:

3612

Cov.:

AF XY:

0.209

AC XY:

15561

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.0897

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.152

Hom.:

398

Bravo

AF:

0.217

Asia WGS

AF:

0.169

AC:

585

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

4.5

Dann

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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