rs878854225
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_001387283.1(SMARCA4):c.4340G>A(p.Arg1447Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,612,602 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). Synonymous variant affecting the same amino acid position (i.e. R1447R) has been classified as Likely benign.
Frequency
Consequence
NM_001387283.1 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 |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.4340G>A | p.Arg1447Gln | missense_variant | 31/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.4244G>A | p.Arg1415Gln | missense_variant | 30/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.4340G>A | p.Arg1447Gln | missense_variant | 31/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.4244G>A | p.Arg1415Gln | missense_variant | 30/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134794
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460420Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726582
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2023 | This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 238465). This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1447 of the SMARCA4 protein (p.Arg1447Gln). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | 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