10-133557909-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001143764.3(SYCE1):c.329G>T(p.Arg110Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,962 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: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
SYCE1
NM_001143764.3 missense
NM_001143764.3 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 0.111
Genes affected
SYCE1 (HGNC:28852): (synaptonemal complex central element protein 1) This gene encodes a member of the synaptonemal complex, which links homologous chromosomes during prophase I of meiosis. The tripartite structure of the complex is highly conserved amongst metazoans. It consists of two lateral elements and a central region formed by transverse elements and a central element. The protein encoded by this gene localizes to the central element and is required for initiation and elongation of the synapsis. Allelic variants of this gene have been associated with premature ovarian failure and spermatogenic failure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
CYP2E1 (HGNC:2631): (cytochrome P450 family 2 subfamily E member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [provided by RefSeq, Jul 2008]
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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=0.11882332).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYCE1 | NM_001143764.3 | c.329G>T | p.Arg110Met | missense_variant | 6/13 | ENST00000343131.7 | |
SYCE1 | NM_001143763.2 | c.329G>T | p.Arg110Met | missense_variant | 6/13 | ||
SYCE1 | NM_130784.4 | c.221G>T | p.Arg74Met | missense_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYCE1 | ENST00000343131.7 | c.329G>T | p.Arg110Met | missense_variant | 6/13 | 1 | NM_001143764.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000139 AC: 35AN: 251464Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135904
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461790Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727186
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74318
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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 | Sep 16, 2021 | The c.329G>T (p.R110M) alteration is located in exon 6 (coding exon 6) of the SYCE1 gene. This alteration results from a G to T substitution at nucleotide position 329, causing the arginine (R) at amino acid position 110 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MutPred
0.32
.;Loss of MoRF binding (P = 0.0148);Loss of MoRF binding (P = 0.0148);
MVP
MPC
0.66
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