chrX-47575235-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_006950.3(SYN1):c.1198G>A(p.Asp400Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000411 in 1,095,139 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D400E) has been classified as Uncertain significance.
Frequency
Consequence
NM_006950.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYN1 | NM_006950.3 | c.1198G>A | p.Asp400Asn | missense_variant | 10/13 | ENST00000295987.13 | |
SYN1 | NM_133499.2 | c.1198G>A | p.Asp400Asn | missense_variant | 10/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYN1 | ENST00000295987.13 | c.1198G>A | p.Asp400Asn | missense_variant | 10/13 | 2 | NM_006950.3 | P3 | |
SYN1 | ENST00000340666.5 | c.1198G>A | p.Asp400Asn | missense_variant | 10/13 | 1 | A1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 exomes AF: 0.00000578 AC: 1AN: 172896Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 58872
GnomAD4 exome AF: 0.0000411 AC: 45AN: 1095139Hom.: 0 Cov.: 32 AF XY: 0.0000526 AC XY: 19AN XY: 360877
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces aspartic acid with asparagine at codon 400 of the SYN1 protein (p.Asp400Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with SYN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 465087). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at