Variant 17-75843090-C-T 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.262-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 673,414 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 89 hom., cov: 32)

Exomes 𝑓: 0.012 ( 133 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.39

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-75843090-C-T is Benign according to our data. Variant chr17-75843090-C-T is described in ClinVar as [Benign]. Clinvar id is 263230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0621 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.262-17G>A		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.262-17G>A		intron_variant		1	NM_199242.3	ENSP00000207549.3		Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3105

AN:

139318

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.00276

Gnomad EAS

AF:

0.0328

Gnomad SAS

AF:

0.0179

Gnomad FIN

AF:

0.000714

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.000806

Gnomad OTH

AF:

0.0178

GnomAD3 exomes

AF:

0.0130

AC:

3138

AN:

241030

Hom.:

AF XY:

0.0110

AC XY:

1456

AN XY:

132372

show subpopulations

Gnomad AFR exome

AF:

0.0669

Gnomad AMR exome

AF:

0.0314

Gnomad ASJ exome

AF:

0.00214

Gnomad EAS exome

AF:

0.0272

Gnomad SAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.000793

Gnomad NFE exome

AF:

0.000845

Gnomad OTH exome

AF:

0.00830

GnomAD4 exome

AF:

0.0118

AC:

6314

AN:

533964

Hom.:

133

Cov.:

AF XY:

0.0107

AC XY:

3107

AN XY:

289386

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0362

Gnomad4 ASJ exome

AF:

0.00455

Gnomad4 EAS exome

AF:

0.0280

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0223

AC:

3110

AN:

139450

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1494

AN XY:

67586

show subpopulations

Gnomad4 AFR

AF:

0.0642

Gnomad4 AMR

AF:

0.0198

Gnomad4 ASJ

AF:

0.00276

Gnomad4 EAS

AF:

0.0328

Gnomad4 SAS

AF:

0.0181

Gnomad4 FIN

AF:

0.000714

Gnomad4 NFE

AF:

0.000806

Gnomad4 OTH

AF:

0.0181

Alfa

AF:

0.00848

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Familial hemophagocytic lymphohistiocytosis 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.73

DANN

Benign

0.57

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