rs201600949
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The ENST00000344626.10(SMARCA4):c.719C>A(p.Pro240Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. P240L) has been classified as Likely benign.
Frequency
Consequence
ENST00000344626.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.719C>A | p.Pro240Gln | missense_variant | 4/36 | ENST00000646693.2 | NP_001374212.1 | |
SMARCA4 | NM_003072.5 | c.719C>A | p.Pro240Gln | missense_variant | 4/35 | ENST00000344626.10 | NP_003063.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.719C>A | p.Pro240Gln | missense_variant | 4/36 | NM_001387283.1 | ENSP00000495368 | |||
SMARCA4 | ENST00000344626.10 | c.719C>A | p.Pro240Gln | missense_variant | 4/35 | 1 | NM_003072.5 | ENSP00000343896 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1386750Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 684462
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The p.P240Q variant (also known as c.719C>A), located in coding exon 3 of the SMARCA4 gene, results from a C to A substitution at nucleotide position 719. The proline at codon 240 is replaced by glutamine, an amino acid with similar properties. Missense and in-frame variants in SMARCA4 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome including small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Jelinic P et al. Nat Genet. 2014 May;46(5):424-6). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, the association of this alteration with Coffin-Siris syndrome is unknown; however, the association of this alteration with rhabdoid tumor predisposition syndrome is unlikely. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at