dbSNP rs3744026: UNC13D:c.1596+36A>G (chr17-75835819-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199242.3(UNC13D):c.1596+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,888 control chromosomes in the GnomAD database, including 21,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 7932 hom., cov: 33)

Exomes 𝑓: 0.094 ( 13430 hom. )

Consequence

UNC13D
NM_199242.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.92

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=-0.98).

BP6

Variant 17-75835819-T-C is Benign according to our data. Variant chr17-75835819-T-C is described in ClinVar as [Benign]. Clinvar id is 263215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13D	NM_199242.3 link	c.1596+36A>G		intron_variant	Intron 18 of 31	ENST00000207549.9	NP_954712.1	Q70J99-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13D	ENST00000207549.9 link	c.1596+36A>G		intron_variant	Intron 18 of 31	1	NM_199242.3	ENSP00000207549.3		Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35095

AN:

152084

Hom.:

7907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0531

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.0684

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.141

AC:

35467

AN:

251240

Hom.:

5109

AF XY:

0.134

AC XY:

18223

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.605

Gnomad AMR exome

AF:

0.0942

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.0511

Gnomad NFE exome

AF:

0.0699

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.0938

AC:

137126

AN:

1461686

Hom.:

13430

Cov.:

AF XY:

0.0948

AC XY:

68923

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.605

Gnomad4 AMR exome

AF:

0.0989

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.0536

Gnomad4 NFE exome

AF:

0.0626

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.231

AC:

35163

AN:

152202

Hom.:

7932

Cov.:

AF XY:

0.228

AC XY:

17002

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.586

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0531

Gnomad4 NFE

AF:

0.0684

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.106

Hom.:

1667

Bravo

AF:

0.254

Asia WGS

AF:

0.233

AC:

809

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.23

DANN

Benign

0.25

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