rs142193069
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_003079.5(SMARCE1):c.1079G>A(p.Gly360Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00276 in 1,613,810 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G360R) has been classified as Likely benign.
Frequency
Consequence
NM_003079.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCE1 | NM_003079.5 | c.1079G>A | p.Gly360Asp | missense_variant | 11/11 | ENST00000348513.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCE1 | ENST00000348513.12 | c.1079G>A | p.Gly360Asp | missense_variant | 11/11 | 1 | NM_003079.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00141 AC: 214AN: 152116Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00147 AC: 368AN: 251080Hom.: 1 AF XY: 0.00157 AC XY: 213AN XY: 135702
GnomAD4 exome AF: 0.00290 AC: 4241AN: 1461576Hom.: 11 Cov.: 31 AF XY: 0.00274 AC XY: 1995AN XY: 727104
GnomAD4 genome ? AF: 0.00141 AC: 214AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.00132 AC XY: 98AN XY: 74432
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | SMARCE1: BS1, BS2 - |
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The SMARCE1 p.Gly360Asp variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs142193069), LOVd 3.0 and in ClinVar (classified as likely benign by Invitae and as a VUS by Genetics Services University of Chicago and Ambry Genetics). The variant was also identified in control databases in 408 of 282474 chromosomes (1 homozygous) at a frequency of 0.001444 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017) and was observed in the following populations: European (non-Finnish) in 328 of 128822 chromosomes (freq: 0.002546), South Asian in 35 of 30614 chromosomes (freq: 0.001143), Other in 8 of 7216 chromosomes (freq: 0.001109), Latino in 18 of 35434 chromosomes (freq: 0.000508), African in 12 of 24968 chromosomes (freq: 0.000481) and European (Finnish) in 7 of 25098 chromosomes (freq: 0.000279); it was not observed in the Ashkenazi Jewish and East Asian populations. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Gly360 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2021 | This variant is associated with the following publications: (PMID: 25169753) - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 10, 2018 | - - |
SMARCE1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2020 | 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). - |
Familial meningioma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2019 | 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