rs762287154
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_003919.3(SGCE):c.905A>T(p.Lys302Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000297 in 1,613,516 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K302N) has been classified as Uncertain significance.
Frequency
Consequence
NM_003919.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCE | NM_003919.3 | c.905A>T | p.Lys302Ile | missense_variant | 7/11 | ENST00000648936.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCE | ENST00000648936.2 | c.905A>T | p.Lys302Ile | missense_variant | 7/11 | NM_003919.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250442Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135338
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461370Hom.: 1 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 726992
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74318
ClinVar
Submissions by phenotype
Myoclonic dystonia 11 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 302 of the SGCE protein (p.Lys302Ile). This variant is present in population databases (rs762287154, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of dystonia and related disorders (Invitae). ClinVar contains an entry for this variant (Variation ID: 532784). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SGCE protein function with a negative predictive value of 80%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 03, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | The c.905A>T (p.K302I) alteration is located in exon 7 (coding exon 7) of the SGCE gene. This alteration results from a A to T substitution at nucleotide position 905, causing the lysine (K) at amino acid position 302 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at