NM_006950.3:c.1699A>G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006950.3(SYN1):c.1699A>G(p.Thr567Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,101,774 control chromosomes in the GnomAD database, including 48 homozygotes. There are 755 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006950.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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SYN1 | ENST00000295987.13 | c.1699A>G | p.Thr567Ala | missense_variant | Exon 12 of 13 | 2 | NM_006950.3 | ENSP00000295987.7 | ||
SYN1 | ENST00000340666.5 | c.1699A>G | p.Thr567Ala | missense_variant | Exon 12 of 13 | 1 | ENSP00000343206.4 | |||
SYN1 | ENST00000640721.1 | c.70+403A>G | intron_variant | Intron 1 of 1 | 5 | ENSP00000492857.1 |
Frequencies
GnomAD3 genomes AF: 0.0135 AC: 1505AN: 111798Hom.: 24 Cov.: 24 AF XY: 0.0125 AC XY: 427AN XY: 34240
GnomAD3 exomes AF: 0.00113 AC: 61AN: 53883Hom.: 1 AF XY: 0.000326 AC XY: 6AN XY: 18429
GnomAD4 exome AF: 0.00122 AC: 1212AN: 989933Hom.: 24 Cov.: 32 AF XY: 0.00103 AC XY: 328AN XY: 318907
GnomAD4 genome AF: 0.0135 AC: 1506AN: 111841Hom.: 24 Cov.: 24 AF XY: 0.0125 AC XY: 427AN XY: 34295
ClinVar
Submissions by phenotype
not provided Benign:6
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SYN1: BS1, BS2 -
not specified Uncertain:1Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Benign:2
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Intellectual disability, X-linked 50 Uncertain:1
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SYN1-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
History of neurodevelopmental disorder Benign:1
General population or sub-population frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign);Subpopulation frequency in support of benign classification -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at