rs7226310

chr17-75840360-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_199242.3(UNC13D):c.754-31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 1,610,762 control chromosomes in the GnomAD database, including 3,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.096 (1238 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2722 hom.)
• Consequence: UNC13D NM_199242.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-75840360-G-A is Benign according to our data. Variant chr17-75840360-G-A is described in ClinVar as [Benign]. Clinvar id is 263244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13D	NM_199242.3	c.754-31C>T		intron_variant		ENST00000207549.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13D	ENST00000207549.9	c.754-31C>T		intron_variant		1	NM_199242.3	P1

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14549 AN: 152020 Hom.: 1232 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0831

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0851

GnomAD3 exomes AF: 0.0579 AC: 14312 AN: 246982 Hom.: 748 AF XY: 0.0580 AC XY: 7773 AN XY: 134098

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.0270

Gnomad ASJ exome AF: 0.0463

Gnomad EAS exome AF: 0.0268

Gnomad SAS exome AF: 0.0937

Gnomad FIN exome AF: 0.0340

Gnomad NFE exome AF: 0.0433

Gnomad OTH exome AF: 0.0534

GnomAD4 exome AF: 0.0495 AC: 72199 AN: 1458626 Hom.: 2722 Cov.: 34 AF XY: 0.0505 AC XY: 36663 AN XY: 725652

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.0461

Gnomad4 EAS exome AF: 0.0375

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.0356

Gnomad4 NFE exome AF: 0.0419

Gnomad4 OTH exome AF: 0.0580

GnomAD4 genome AF: 0.0958 AC: 14575 AN: 152136 Hom.: 1238 Cov.: 32 AF XY: 0.0948 AC XY: 7052 AN XY: 74388

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0456

Gnomad4 OTH AF: 0.0837

Alfa AF: 0.0724 Hom.: 141

Bravo AF: 0.102

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.59
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs7226310; hg19: chr17-73836441; COSMIC: COSV52884447; COSMIC: COSV52884447;