chr17-75830039-C-T

Position:

chr17-75830039-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_199242.3(UNC13D):c.2943G>A(p.Glu981=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 1,577,316 control chromosomes in the GnomAD database, including 2,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 558 hom., cov: 32)

Exomes 𝑓: 0.047 ( 2009 hom. )

Consequence

UNC13D
NM_199242.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.18

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 17-75830039-C-T is Benign according to our data. Variant chr17-75830039-C-T is described in ClinVar as [Benign]. Clinvar id is 263238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75830039-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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.2943G>A	p.Glu981=	synonymous_variant	30/32	ENST00000207549.9	NP_954712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13D	ENST00000207549.9 linkuse as main transcript	c.2943G>A	p.Glu981=	synonymous_variant	30/32	1	NM_199242.3	ENSP00000207549	P1	Q70J99-1

Frequencies

GnomAD3 genomes

AF:

0.0713

AC:

10845

AN:

152156

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0430

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.0260

Gnomad SAS

AF:

0.0835

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0454

Gnomad OTH

AF:

0.0592

GnomAD3 exomes

AF:

0.0516

AC:

9828

AN:

190444

Hom.:

359

AF XY:

0.0536

AC XY:

5443

AN XY:

101626

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0232

Gnomad ASJ exome

AF:

0.0588

Gnomad EAS exome

AF:

0.0270

Gnomad SAS exome

AF:

0.0924

Gnomad FIN exome

AF:

0.0336

Gnomad NFE exome

AF:

0.0429

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0471

AC:

67125

AN:

1425042

Hom.:

2009

Cov.:

AF XY:

0.0485

AC XY:

34184

AN XY:

705126

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.0262

Gnomad4 ASJ exome

AF:

0.0575

Gnomad4 EAS exome

AF:

0.0375

Gnomad4 SAS exome

AF:

0.0903

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.0531

GnomAD4 genome

AF:

0.0713

AC:

10862

AN:

152274

Hom.:

558

Cov.:

AF XY:

0.0709

AC XY:

5275

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.0430

Gnomad4 ASJ

AF:

0.0634

Gnomad4 EAS

AF:

0.0261

Gnomad4 SAS

AF:

0.0838

Gnomad4 FIN

AF:

0.0342

Gnomad4 NFE

AF:

0.0454

Gnomad4 OTH

AF:

0.0581

Alfa

AF:

0.0599

Hom.:

156

Bravo

AF:

0.0730

Asia WGS

AF:

0.0570

AC:

200

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial hemophagocytic lymphohistiocytosis 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.40

CADD

Benign

9.0

DANN

Benign

0.85

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