11-61533045-C-T

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

5
14

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]

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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
SYT7NM_001365809.2 linkc.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
SYT7ENST00000539008.6 linkc.1144G>A p.Glu382Lys missense_variant Exon 8 of 13 5 NM_001365809.2 ENSP00000439694.1 O43581-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461132
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
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.:
32

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
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;.;.;.;.;.;.
Eigen
Benign
-0.059
Eigen_PC
Benign
0.074
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.94
D;D;D;D;D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.29
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;.;.;.;.;.;.
PrimateAI
Uncertain
0.62
T
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
D
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.

Other links and lift over

hg19: chr11-61300517; API