chr11-45255884-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020826.3(SYT13):c.191T>G(p.Val64Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000216 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
SYT13
NM_020826.3 missense
NM_020826.3 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.71
Genes affected
SYT13 (HGNC:14962): (synaptotagmin 13) This gene encodes a member of the large synaptotagmin protein family. Family members have an extracellular N-terminal transmembrane domain and a cytoplasmic C terminus with two tandem C2 domains (C2A and C2B). Synaptotogmin family members can form homo- and heteromeric complexes with each other. They also have different biochemical properties and developmental profiles, and patterns of tissue distribution. Synaptotagmins function as membrane traffickers in multicellular organisms. Two alternatively spliced transcript variants that encode different protein isoforms have been described 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=0.21757847).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYT13 | NM_020826.3 | c.191T>G | p.Val64Gly | missense_variant | 2/6 | ENST00000020926.8 | |
SYT13 | NM_001247987.2 | c.-242T>G | 5_prime_UTR_variant | 4/8 | |||
SYT13 | XM_047427338.1 | c.-242T>G | 5_prime_UTR_variant | 2/6 | |||
SYT13 | XM_047427339.1 | c.-242T>G | 5_prime_UTR_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYT13 | ENST00000020926.8 | c.191T>G | p.Val64Gly | missense_variant | 2/6 | 1 | NM_020826.3 | P1 | |
SYT13 | ENST00000533332.1 | c.*208T>G | 3_prime_UTR_variant, NMD_transcript_variant | 4/8 | 1 | ||||
SYT13 | ENST00000528101.1 | c.71T>G | p.Val24Gly | missense_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000758 AC: 19AN: 250756Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135588
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GnomAD4 exome AF: 0.000229 AC: 335AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 166AN XY: 727232
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74314
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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 | Aug 12, 2021 | The c.191T>G (p.V64G) alteration is located in exon 2 (coding exon 2) of the SYT13 gene. This alteration results from a T to G substitution at nucleotide position 191, causing the valine (V) at amino acid position 64 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at