chr21-32639778-G-A
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_203446.3(SYNJ1):c.3590C>T(p.Thr1197Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,612,648 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1197T) has been classified as Likely benign.
Frequency
Consequence
NM_203446.3 missense, splice_region
Scores
Clinical Significance
Conservation
Publications
- genetic developmental and epileptic encephalopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- developmental and epileptic encephalopathy, 53Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- early-onset Parkinson disease 20Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- undetermined early-onset epileptic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- atypical juvenile parkinsonismInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- young-onset Parkinson diseaseInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00193 AC: 293AN: 152160Hom.: 2 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00148 AC: 371AN: 250702 AF XY: 0.00139 show subpopulations
GnomAD4 exome AF: 0.00196 AC: 2857AN: 1460370Hom.: 5 Cov.: 29 AF XY: 0.00185 AC XY: 1346AN XY: 726622 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00193 AC: 294AN: 152278Hom.: 2 Cov.: 32 AF XY: 0.00172 AC XY: 128AN XY: 74460 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:6
This variant is associated with the following publications: (PMID: 27393345) -
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SYNJ1: BS2 -
Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Benign:1
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SYNJ1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at