Variant rs2290768 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.2709+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,576,936 control chromosomes in the GnomAD database, including 14,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4281 hom., cov: 33)

Exomes 𝑓: 0.091 ( 10053 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.23

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=-0.87).

BP6

Variant 17-75830530-G-A is Benign according to our data. Variant chr17-75830530-G-A is described in ClinVar as [Benign]. Clinvar id is 263233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 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.2709+48C>T		intron_variant		ENST00000207549.9	NP_954712.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
UNC13D	ENST00000207549.9 linkuse as main transcript	c.2709+48C>T	intron_variant	1	NM_199242.3	ENSP00000207549	P1	Q70J99-1
UNC13D	ENST00000412096.6 linkuse as main transcript	c.2709+48C>T	intron_variant	2		ENSP00000388093		Q70J99-3
UNC13D	ENST00000699510.1 linkuse as main transcript	c.1575+48C>T	intron_variant			ENSP00000514405
UNC13D	ENST00000590856.1 linkuse as main transcript	n.84+48C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27635

AN:

152074

Hom.:

4253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0543

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.0716

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.135

AC:

25453

AN:

188306

Hom.:

2688

AF XY:

0.132

AC XY:

13323

AN XY:

100700

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.315

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.0530

Gnomad NFE exome

AF:

0.0750

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.0914

AC:

130253

AN:

1424744

Hom.:

10053

Cov.:

AF XY:

0.0930

AC XY:

65568

AN XY:

705264

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.327

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.0552

Gnomad4 NFE exome

AF:

0.0657

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.182

AC:

27703

AN:

152192

Hom.:

4281

Cov.:

AF XY:

0.181

AC XY:

13435

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.177

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.0543

Gnomad4 NFE

AF:

0.0716

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.136

Hom.:

621

Bravo

AF:

0.199

Asia WGS

AF:

0.219

AC:

763

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

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.061

DANN

Benign

0.58

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