Variant 11-7252305-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000318881.11(SYT9):c.119G>A(p.Arg40His) variant causes a missense change. The variant allele was found at a frequency of 0.00000296 in 1,352,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

SYT9
ENST00000318881.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29667234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT9	NM_175733.4 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	1/7	ENST00000318881.11	NP_783860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SYT9	ENST00000318881.11 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	1/7	1	NM_175733.4	ENSP00000324419	P1
SYT9	ENST00000532592.1 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant, NMD_transcript_variant	1/6	2		ENSP00000434558
SYT9	ENST00000524820.6 linkuse as main transcript	c.49+13389G>A		intron_variant, NMD_transcript_variant		2		ENSP00000432141

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000296

AC:

AN:

1352934

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

666804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000283

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.119G>A (p.R40H) alteration is located in exon 1 (coding exon 1) of the SYT9 gene. This alteration results from a G to A substitution at nucleotide position 119, causing the arginine (R) at amino acid position 40 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.033

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.73

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.88

REVEL

Benign

0.12

Sift

Benign

0.034

Sift4G

Uncertain

0.026

Polyphen

0.89

Vest4

0.17

MutPred

0.38

Loss of sheet (P = 0.0104);

MVP

0.56

MPC

0.67

ClinPred

0.43

GERP RS

2.8

Varity_R

0.069

gMVP

0.35

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over