Variant rs112501005 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_199242.3(UNC13D):c.1390-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,613,048 control chromosomes in the GnomAD database, including 605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 69 hom., cov: 33)

Exomes 𝑓: 0.025 ( 536 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.710

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-75836294-A-G is Benign according to our data. Variant chr17-75836294-A-G is described in ClinVar as [Benign]. Clinvar id is 263213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-75836294-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.028 (4270/152306) while in subpopulation AFR AF= 0.0433 (1801/41568). AF 95% confidence interval is 0.0417. There are 69 homozygotes in gnomad4. There are 1940 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13D	NM_199242.3 linkuse as main transcript	c.1390-38T>C		intron_variant		ENST00000207549.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13D	ENST00000207549.9 linkuse as main transcript	c.1390-38T>C		intron_variant		1	NM_199242.3	P1	Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4252

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.00649

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0373

GnomAD3 exomes

AF:

0.0227

AC:

5633

AN:

247868

Hom.:

AF XY:

0.0231

AC XY:

3110

AN XY:

134460

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0392

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0261

Gnomad FIN exome

AF:

0.00576

Gnomad NFE exome

AF:

0.0255

Gnomad OTH exome

AF:

0.0247

GnomAD4 exome

AF:

0.0254

AC:

37145

AN:

1460742

Hom.:

536

Cov.:

AF XY:

0.0253

AC XY:

18403

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.0384

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.0376

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.00724

Gnomad4 NFE exome

AF:

0.0268

Gnomad4 OTH exome

AF:

0.0245

GnomAD4 genome

AF:

0.0280

AC:

4270

AN:

152306

Hom.:

Cov.:

AF XY:

0.0261

AC XY:

1940

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0433

Gnomad4 AMR

AF:

0.0205

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.00649

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0300

Hom.:

Bravo

AF:

0.0297

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.91

CADD

Benign

1.1

DANN

Benign

0.44

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