rs1361910224
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001387283.1(SMARCA4):c.973G>A(p.Val325Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000813 in 1,598,980 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V325L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001387283.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.973G>A | p.Val325Met | missense_variant | 6/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.973G>A | p.Val325Met | missense_variant | 6/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.973G>A | p.Val325Met | missense_variant | 6/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.973G>A | p.Val325Met | missense_variant | 6/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151700Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000189 AC: 4AN: 211906Hom.: 0 AF XY: 0.0000257 AC XY: 3AN XY: 116774
GnomAD4 exome AF: 0.00000760 AC: 11AN: 1447280Hom.: 0 Cov.: 34 AF XY: 0.00000974 AC XY: 7AN XY: 718856
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151700Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74040
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2023 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 325 of the SMARCA4 protein (p.Val325Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 480591). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 04, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 01, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2022 | 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. - |
Intellectual disability, autosomal dominant 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at