rs3744959

chr18-43270331-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020783.4(SYT4):c.*10C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 1,609,170 control chromosomes in the GnomAD database, including 11,834 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.090 (1099 hom., cov: 32)
  • Exomes 𝑓: 0.099 (10735 hom.)
• Consequence: SYT4 NM_020783.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

Genes affected

SYT4 (HGNC:11512): (synaptotagmin 4) Predicted to enable several functions, including calcium ion binding activity; phospholipid binding activity; and syntaxin binding activity. Involved in negative regulation of catecholamine secretion and positive regulation of dendrite extension. Predicted to be located in several cellular components, including microvesicle; perinuclear region of cytoplasm; and secretory vesicle. Predicted to be active in several cellular components, including axon; exocytic vesicle; and glutamatergic synapse. Predicted to be integral component of neuronal dense core vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT4	NM_020783.4	c.*10C>T		3_prime_UTR_variant	4/4	ENST00000255224.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT4	ENST00000255224.8	c.*10C>T		3_prime_UTR_variant	4/4	1	NM_020783.4	P1
SYT4	ENST00000585604.1	n.596C>T		non_coding_transcript_exon_variant	3/3	1
SYT4	ENST00000590752.5	c.*10C>T		3_prime_UTR_variant	4/4	2
SYT4	ENST00000586678.1	n.478C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13684 AN: 151976 Hom.: 1092 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.0727

GnomAD3 exomes AF: 0.131 AC: 32835 AN: 250078 Hom.: 3734 AF XY: 0.123 AC XY: 16604 AN XY: 135088

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.0325

Gnomad EAS exome AF: 0.402

Gnomad SAS exome AF: 0.0848

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0838

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0986 AC: 143670 AN: 1457076 Hom.: 10735 Cov.: 31 AF XY: 0.0971 AC XY: 70283 AN XY: 723896

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.0322

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.0846

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0848

Gnomad4 OTH exome AF: 0.0951

GnomAD4 genome AF: 0.0900 AC: 13696 AN: 152094 Hom.: 1099 Cov.: 32 AF XY: 0.0936 AC XY: 6953 AN XY: 74312

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0827 Hom.: 1127

Bravo AF: 0.0966

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.0
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs3744959; hg19: chr18-40850296; COSMIC: COSV54898400; COSMIC: COSV54898400;