rs772153816
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBS1_SupportingBS2
The NM_003072.5(SMARCA4):c.4258G>A(p.Gly1420Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,460,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003072.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.4354G>A | p.Gly1452Ser | missense_variant | Exon 31 of 36 | ENST00000646693.2 | NP_001374212.1 | |
SMARCA4 | NM_003072.5 | c.4258G>A | p.Gly1420Ser | missense_variant | Exon 30 of 35 | ENST00000344626.10 | NP_003063.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.4354G>A | p.Gly1452Ser | missense_variant | Exon 31 of 36 | NM_001387283.1 | ENSP00000495368.1 | |||
SMARCA4 | ENST00000344626.10 | c.4258G>A | p.Gly1420Ser | missense_variant | Exon 30 of 35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
SMARCA4 | ENST00000643549.1 | c.4264G>A | p.Gly1422Ser | missense_variant | Exon 30 of 35 | ENSP00000493975.1 | ||||
SMARCA4 | ENST00000541122.6 | c.4168G>A | p.Gly1390Ser | missense_variant | Exon 30 of 35 | 5 | ENSP00000445036.2 | |||
SMARCA4 | ENST00000643296.1 | c.4168G>A | p.Gly1390Ser | missense_variant | Exon 29 of 34 | ENSP00000496635.1 | ||||
SMARCA4 | ENST00000644737.1 | c.4168G>A | p.Gly1390Ser | missense_variant | Exon 29 of 34 | ENSP00000495548.1 | ||||
SMARCA4 | ENST00000589677.5 | c.4168G>A | p.Gly1390Ser | missense_variant | Exon 30 of 35 | 5 | ENSP00000464778.1 | |||
SMARCA4 | ENST00000643995.1 | c.3679G>A | p.Gly1227Ser | missense_variant | Exon 27 of 32 | ENSP00000496004.1 | ||||
SMARCA4 | ENST00000644963.1 | c.2911G>A | p.Gly971Ser | missense_variant | Exon 23 of 28 | ENSP00000495599.1 | ||||
SMARCA4 | ENST00000644065.1 | c.2893G>A | p.Gly965Ser | missense_variant | Exon 22 of 27 | ENSP00000493615.1 | ||||
SMARCA4 | ENST00000642350.1 | c.2752G>A | p.Gly918Ser | missense_variant | Exon 22 of 27 | ENSP00000495355.1 | ||||
SMARCA4 | ENST00000643857.1 | c.2620G>A | p.Gly874Ser | missense_variant | Exon 21 of 25 | ENSP00000494159.1 | ||||
SMARCA4 | ENST00000538456.4 | c.424G>A | p.Gly142Ser | missense_variant | Exon 4 of 8 | 3 | ENSP00000495197.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247528Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134484
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460266Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726516
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 16 Uncertain:2
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Rhabdoid tumor predisposition syndrome 2 Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1452 of the SMARCA4 protein (p.Gly1452Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 408697). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMARCA4 protein function. 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. -
not provided Uncertain:1
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32686686) -
Hereditary cancer-predisposing syndrome Benign:1
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