11-61533113-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365809.2(SYT7):​c.1076G>A​(p.Gly359Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SYT7
NM_001365809.2 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYT7NM_001365809.2 linkc.1076G>A p.Gly359Glu missense_variant Exon 8 of 13 ENST00000539008.6 NP_001352738.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYT7ENST00000539008.6 linkc.1076G>A p.Gly359Glu missense_variant Exon 8 of 13 5 NM_001365809.2 ENSP00000439694.1 O43581-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.227G>A (p.G76E) 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 227, causing the glycine (G) at amino acid position 76 to be replaced by a glutamic acid (E). 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
0.24
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.;.;.;.;.;.
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D;D;D;D;D;D
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.49
T;T;T;T;T;T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.4
L;.;.;.;.;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-2.0
N;N;D;N;D;D;N
REVEL
Benign
0.20
Sift
Uncertain
0.0030
D;D;D;T;D;D;D
Sift4G
Benign
0.37
T;T;D;T;D;T;.
Polyphen
1.0
D;.;.;.;.;.;.
Vest4
0.66
MutPred
0.24
Loss of catalytic residue at A75 (P = 0.0511);.;.;.;.;.;Loss of catalytic residue at A75 (P = 0.0511);
MVP
0.73
MPC
2.1
ClinPred
0.91
D
GERP RS
4.6
Varity_R
0.29
gMVP
0.68

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.

Other links and lift over

hg19: chr11-61300585; API