Genetic Variant 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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175733.4. 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
	SYT9	NM_175733.4	MANE Select	c.1166-95G>T		intron	N/A	NP_783860.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SYT9	ENST00000318881.11	TSL:1 MANE Select	c.1166-95G>T	intron	N/A	ENSP00000324419.6
SYT9	ENST00000524820.6	TSL:2	n.*263-95G>T	intron	N/A	ENSP00000432141.2
SYT9	ENST00000532592.1	TSL:2	n.*97-95G>T	intron	N/A	ENSP00000434558.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over