chrX-49193294-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_003179.3(SYP):c.593C>T(p.Thr198Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,210,853 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000080 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.00011 ( 0 hom. 38 hem. )
Consequence
SYP
NM_003179.3 missense
NM_003179.3 missense
Scores
5
11
Clinical Significance
Conservation
PhyloP100: 3.33
Genes affected
SYP (HGNC:11506): (synaptophysin) This gene encodes an integral membrane protein of small synaptic vesicles in brain and endocrine cells. The protein also binds cholesterol and is thought to direct targeting of vesicle-associated membrane protein 2 (synaptobrevin) to intracellular compartments. Mutations in this gene are associated with an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08850497).
BP6
?
Variant X-49193294-G-A is Benign according to our data. Variant chrX-49193294-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 282601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-49193294-G-A is described in Lovd as [Benign]. Variant chrX-49193294-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000111 (122/1097982) while in subpopulation NFE AF= 0.000143 (120/842030). AF 95% confidence interval is 0.000122. There are 0 homozygotes in gnomad4_exome. There are 38 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYP | NM_003179.3 | c.593C>T | p.Thr198Ile | missense_variant | 5/7 | ENST00000263233.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYP | ENST00000263233.9 | c.593C>T | p.Thr198Ile | missense_variant | 5/7 | 1 | NM_003179.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000798 AC: 9AN: 112816Hom.: 0 Cov.: 24 AF XY: 0.0000572 AC XY: 2AN XY: 34948
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000137 AC: 25AN: 181833Hom.: 0 AF XY: 0.000180 AC XY: 12AN XY: 66491
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GnomAD4 exome AF: 0.000111 AC: 122AN: 1097982Hom.: 0 Cov.: 32 AF XY: 0.000105 AC XY: 38AN XY: 363346
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GnomAD4 genome ? AF: 0.0000797 AC: 9AN: 112871Hom.: 0 Cov.: 24 AF XY: 0.0000571 AC XY: 2AN XY: 35013
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 13, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
P;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