19-55173672-C-A

Variant names:

• chr19-55173672-C-A
• rs778464518
• NM_003180.3:c.973G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003180.3(SYT5):​c.973G>T​(p.Glu325*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000237 in 1,268,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: SYT5 NM_003180.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

Genes affected

SYT5 (HGNC:11513): (synaptotagmin 5) Synaptotagmins, such as SYT5, are a family of type III membrane proteins characterized by cytoplasmic repeats related to protein kinase C (see MIM 176960) regulatory (C2) domains, which are thought to bind calcium. Synaptotagmins may act both as negative regulators of vesicle fusion, allowing fusion in the presence of calcium, and as calcium receptors or sensor molecules (summary by Hudson and Birnbaum, 1995 [PubMed 7597049]).[supplied by OMIM, Feb 2011]

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003180.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT5	NM_003180.3	MANE Select	c.973G>T	p.Glu325*	stop_gained	Exon 9 of 9	NP_003171.2	O00445-1
	SYT5	NM_001297774.2		c.961G>T	p.Glu321*	stop_gained	Exon 7 of 7	NP_001284703.1	O00445-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT5	ENST00000354308.8	TSL:1 MANE Select	c.973G>T	p.Glu325*	stop_gained	Exon 9 of 9	ENSP00000346265.2	O00445-1
	SYT5	ENST00000537500.5	TSL:2	c.973G>T	p.Glu325*	stop_gained	Exon 8 of 8	ENSP00000442896.1	O00445-1
	SYT5	ENST00000868688.1		c.973G>T	p.Glu325*	stop_gained	Exon 9 of 9	ENSP00000538747.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000237 AC: 3 AN: 1268118 Hom.: 0 Cov.: 31 AF XY: 0.00000323 AC XY: 2 AN XY: 620078

African (AFR) AF: 0.00 AC: 0 AN: 24810

American (AMR) AF: 0.00 AC: 0 AN: 14712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19918

East Asian (EAS) AF: 0.00 AC: 0 AN: 27898

South Asian (SAS) AF: 0.00 AC: 0 AN: 61862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4240

European-Non Finnish (NFE) AF: 0.00000295 AC: 3 AN: 1016134

Other (OTH) AF: 0.00 AC: 0 AN: 51722

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	52
DANN	Uncertain	1.0
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		4.8
Vest4		0.070
GERP RS		3.2
Mutation Taster		=37/163	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs778464518; hg19: chr19-55685040;