Genetic Variant SYT7:p.Glu382Lys (chr11-61533045-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001365809.2(SYT7):c.1144G>A(p.Glu382Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,132 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: 0.0000021 ( 0 hom. )

Consequence

SYT7
NM_001365809.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

Variant links:

Genes affected

SYT7 (HGNC:11514): (synaptotagmin 7) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. A similar protein in rodents mediates hormone secretion and lysosome exocytosis. In humans, expression of this gene has been associated with prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

SYT7 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=0.28992176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT7	NM_001365809.2 link	c.1144G>A	p.Glu382Lys	missense_variant	Exon 8 of 13	ENST00000539008.6	NP_001352738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT7	ENST00000539008.6 link	c.1144G>A	p.Glu382Lys	missense_variant	Exon 8 of 13	5	NM_001365809.2	ENSP00000439694.1		O43581-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461132

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726912

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

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

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.295G>A (p.E99K) alteration is located in exon 4 (coding exon 4) of the SYT7 gene. This alteration results from a G to A substitution at nucleotide position 295, causing the glutamic acid (E) at amino acid position 99 to be replaced by a lysine (K). 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

0.29

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;.;.;.;.;.

Eigen

Benign

-0.059

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.29

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.;.;.;.;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N

REVEL

Benign

0.095

Sift

Benign

0.036

D;D;D;T;D;D;D

Sift4G

Benign

0.21

T;T;T;T;T;T;.

Polyphen

0.63

P;.;.;.;.;.;.

Vest4

0.54

MutPred

0.34

Gain of ubiquitination at E99 (P = 0.0025);.;.;.;.;.;Gain of ubiquitination at E99 (P = 0.0025);

MVP

0.84

MPC

1.2

ClinPred

0.82

GERP RS

4.5

Varity_R

0.16

gMVP

0.43

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