rs146563315

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365809.2(SYT7):​c.713G>T​(p.Arg238Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000522 in 1,532,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R238Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SYT7
NM_001365809.2 missense

Scores

1
2
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19505385).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYT7NM_001365809.2 linkc.713G>T p.Arg238Leu missense_variant Exon 6 of 13 ENST00000539008.6 NP_001352738.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYT7ENST00000539008.6 linkc.713G>T p.Arg238Leu missense_variant Exon 6 of 13 5 NM_001365809.2 ENSP00000439694.1 O43581-3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152126
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000230
AC:
3
AN:
130558
Hom.:
0
AF XY:
0.0000280
AC XY:
2
AN XY:
71426
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000290
AC:
4
AN:
1380462
Hom.:
0
Cov.:
33
AF XY:
0.00000440
AC XY:
3
AN XY:
681124
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152126
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
23
DANN
Uncertain
0.99
Eigen
Benign
0.062
Eigen_PC
Benign
0.084
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.81
T;T
M_CAP
Pathogenic
0.52
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.96
T
PROVEAN
Benign
-0.45
N;N
REVEL
Benign
0.046
Sift
Uncertain
0.018
D;D
Sift4G
Benign
0.081
T;T
Vest4
0.17
MutPred
0.38
.;Loss of MoRF binding (P = 0.0262);
MVP
0.28
ClinPred
0.11
T
GERP RS
2.9

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146563315; hg19: chr11-61309911; API