dbSNP rs3744959: SYT4:n.596C>T (chr18-43270331-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158

Publications

12 publications found

Variant links:

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]

SYT4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT4	NM_020783.4 link	c.*10C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000255224.8	NP_065834.1	Q9H2B2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT4	ENST00000255224.8 link	c.*10C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_020783.4	ENSP00000255224.2		Q9H2B2-1

Frequencies

GnomAD3 genomes

AF:

0.0900

AC:

13684

AN:

151976

Hom.:

1092

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0971

AC XY:

70283

AN XY:

723896

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

6148

12296

18444

24592

30740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3732

7464

11196

14928

18660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0900

AC:

13696

AN:

152094

Hom.:

1099

Cov.:

AF XY:

0.0936

AC XY:

6953

AN XY:

74312

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0839

AC:

5706

AN:

68000

Other (OTH)

AF:

0.0766

AC:

162

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

591

1182

1774

2365

2956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.0

(source)

DANN

Benign

0.78

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over