ENST00000585604.1:n.596C>T

Variant names:

• chr18-43270331-G-A
• rs3744959
• ENST00000585604.1:n.596C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000585604.1(SYT4):​n.596C>T variant causes a non coding transcript exon 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 ENST00000585604.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000585604.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT4	NM_020783.4	MANE Select	c.*10C>T		3_prime_UTR	Exon 4 of 4	NP_065834.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT4	ENST00000585604.1	TSL:1	n.596C>T		non_coding_transcript_exon	Exon 3 of 3
	SYT4	ENST00000255224.8	TSL:1 MANE Select	c.*10C>T		3_prime_UTR	Exon 4 of 4	ENSP00000255224.2
	SYT4	ENST00000586678.1	TSL:5	n.478C>T		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.131 AC: 32835 AN: 250078 AF XY: 0.123

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 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

African (AFR) AF: 0.0170 AC: 566 AN: 33362

American (AMR) AF: 0.274 AC: 12231 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.0322 AC: 837 AN: 25982

East Asian (EAS) AF: 0.438 AC: 17324 AN: 39574

South Asian (SAS) AF: 0.0846 AC: 7287 AN: 86106

European-Finnish (FIN) AF: 0.104 AC: 5553 AN: 53340

Middle Eastern (MID) AF: 0.0340 AC: 192 AN: 5646

European-Non Finnish (NFE) AF: 0.0848 AC: 93955 AN: 1108280

Other (OTH) AF: 0.0951 AC: 5725 AN: 60202

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

African (AFR) AF: 0.0255 AC: 1058 AN: 41498

American (AMR) AF: 0.203 AC: 3101 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2049 AN: 5154

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4820

European-Finnish (FIN) AF: 0.0953 AC: 1007 AN: 10568

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0839 AC: 5706 AN: 68000

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0836 Hom.: 1415

Bravo AF: 0.0966

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.78
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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