dbSNP rs4757993: SYT9:c.1166-95G>T (chr11-7417862-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_175733.4(SYT9):c.1166-95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,330,030 control chromosomes in the GnomAD database, including 209,815 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 0.49 ( 19325 hom., cov: 31)

Exomes 𝑓: 0.56 ( 190490 hom. )

Consequence

SYT9
NM_175733.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

Publications

6 publications found

Variant links:

Genes affected

SYT9 (HGNC:19265): (synaptotagmin 9) Predicted to enable several functions, including calcium ion binding activity; phospholipid binding activity; and syntaxin binding activity. Predicted to be involved in calcium-ion regulated exocytosis; cellular response to calcium ion; and regulation of secretion by cell. Predicted to be located in clathrin-coated endocytic vesicle membrane. Predicted to be active in hippocampal mossy fiber to CA3 synapse; plasma membrane; and secretory vesicle. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYT9 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT9	NM_175733.4 link	c.1166-95G>T		intron_variant	Intron 4 of 6	ENST00000318881.11	NP_783860.1	Q86SS6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYT9	ENST00000318881.11 link	c.1166-95G>T	intron_variant	Intron 4 of 6	1	NM_175733.4	ENSP00000324419.6	Q86SS6
SYT9	ENST00000524820.6 link	n.*263-95G>T	intron_variant	Intron 5 of 8	2		ENSP00000432141.2	E9PDN4
SYT9	ENST00000532592.1 link	n.*97-95G>T	intron_variant	Intron 3 of 5	2		ENSP00000434558.1	B3KNT7

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73738

AN:

151882

Hom.:

19321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.560

AC:

659314

AN:

1178030

Hom.:

190490

AF XY:

0.559

AC XY:

327244

AN XY:

585658

show subpopulations

African (AFR)

AF:

0.310

AC:

8131

AN:

26248

American (AMR)

AF:

0.366

AC:

10501

AN:

28704

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

13505

AN:

18992

East Asian (EAS)

AF:

0.197

AC:

7103

AN:

36100

South Asian (SAS)

AF:

0.449

AC:

29014

AN:

64570

European-Finnish (FIN)

AF:

0.529

AC:

23698

AN:

44820

Middle Eastern (MID)

AF:

0.591

AC:

2794

AN:

4728

European-Non Finnish (NFE)

AF:

0.595

AC:

537486

AN:

903788

Other (OTH)

AF:

0.541

AC:

27082

AN:

50080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

13332

26664

39996

53328

66660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14050

28100

42150

56200

70250

<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:

0.485

AC:

73772

AN:

152000

Hom.:

19325

Cov.:

AF XY:

0.480

AC XY:

35641

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.319

AC:

13206

AN:

41456

American (AMR)

AF:

0.465

AC:

7104

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

2457

AN:

3472

East Asian (EAS)

AF:

0.187

AC:

966

AN:

5162

South Asian (SAS)

AF:

0.431

AC:

2072

AN:

4802

European-Finnish (FIN)

AF:

0.539

AC:

5691

AN:

10564

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.594

AC:

40403

AN:

67962

Other (OTH)

AF:

0.530

AC:

1117

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1802

3603

5405

7206

9008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.566

Hom.:

41005

Bravo

AF:

0.467

Asia WGS

AF:

0.286

AC:

997

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.074

(source)

DANN

Benign

0.46

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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