Genetic Variant SYT9:c.1467+22506T>C (chr11-7443141-T-C) – 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.1467+22506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,016 control chromosomes in the GnomAD database, including 15,872 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 0.42 ( 15872 hom., cov: 32)

Consequence

SYT9
NM_175733.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0500

Publications

3 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:

SYT9-AS1 (HGNC:56173): (SYT9 antisense RNA 1)

SYT9-AS1 links:

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new If you want to explore the variant's impact on the transcript NM_175733.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 (AFR) allele frequency at 95% confidence interval = 0.695 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT9	NM_175733.4	MANE Select	c.1467+22506T>C		intron	N/A	NP_783860.1	Q86SS6
	SYT9-AS1	NR_103855.1		n.416-1422A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYT9	ENST00000318881.11	TSL:1 MANE Select	c.1467+22506T>C	intron	N/A	ENSP00000324419.6	Q86SS6
SYT9-AS1	ENST00000504206.6	TSL:3	n.341-1422A>G	intron	N/A
SYT9	ENST00000524820.6	TSL:2	n.*686-1048T>C	intron	N/A	ENSP00000432141.2	E9PDN4

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63197

AN:

151898

Hom.:

15825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.417

AC:

63317

AN:

152016

Hom.:

15872

Cov.:

AF XY:

0.405

AC XY:

30134

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.702

AC:

29070

AN:

41434

American (AMR)

AF:

0.282

AC:

4312

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1135

AN:

3470

East Asian (EAS)

AF:

0.242

AC:

1249

AN:

5156

South Asian (SAS)

AF:

0.263

AC:

1265

AN:

4818

European-Finnish (FIN)

AF:

0.233

AC:

2469

AN:

10574

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.332

AC:

22546

AN:

67960

Other (OTH)

AF:

0.400

AC:

844

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1612

3224

4835

6447

8059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.397

Hom.:

12960

Bravo

AF:

0.430

Asia WGS

AF:

0.289

AC:

1010

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

4.1

(source)

DANN

Benign

0.47

PhyloP100

-0.050

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over