chr19-11060078-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4BS1_SupportingBS2
The NM_003072.5(SMARCA4):c.4802G>A(p.Arg1601Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,401,898 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 -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.4898G>A | p.Arg1633Gln | missense_variant | 35/36 | NM_001387283.1 | ENSP00000495368.1 | |||
SMARCA4 | ENST00000344626.10 | c.4802G>A | p.Arg1601Gln | missense_variant | 34/35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
SMARCA4 | ENST00000643549.1 | c.4808G>A | p.Arg1603Gln | missense_variant | 34/35 | ENSP00000493975.1 | ||||
SMARCA4 | ENST00000541122.6 | c.4712G>A | p.Arg1571Gln | missense_variant | 34/35 | 5 | ENSP00000445036.2 | |||
SMARCA4 | ENST00000643296.1 | c.4712G>A | p.Arg1571Gln | missense_variant | 33/34 | ENSP00000496635.1 | ||||
SMARCA4 | ENST00000644737.1 | c.4712G>A | p.Arg1571Gln | missense_variant | 33/34 | ENSP00000495548.1 | ||||
SMARCA4 | ENST00000589677.5 | c.4709G>A | p.Arg1570Gln | missense_variant | 34/35 | 5 | ENSP00000464778.1 | |||
SMARCA4 | ENST00000643995.1 | c.4223G>A | p.Arg1408Gln | missense_variant | 31/32 | ENSP00000496004.1 | ||||
SMARCA4 | ENST00000644963.1 | c.3452G>A | p.Arg1151Gln | missense_variant | 27/28 | ENSP00000495599.1 | ||||
SMARCA4 | ENST00000644065.1 | c.3434G>A | p.Arg1145Gln | missense_variant | 26/27 | ENSP00000493615.1 | ||||
SMARCA4 | ENST00000642350.1 | c.3296G>A | p.Arg1099Gln | missense_variant | 26/27 | ENSP00000495355.1 | ||||
SMARCA4 | ENST00000643857.1 | c.3062G>A | p.Arg1021Gln | missense_variant | 24/25 | ENSP00000494159.1 | ||||
SMARCA4 | ENST00000538456.4 | c.866G>A | p.Arg289Gln | missense_variant | 7/8 | 3 | ENSP00000495197.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000632 AC: 1AN: 158124Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 83580
GnomAD4 exome AF: 0.00000357 AC: 5AN: 1401898Hom.: 0 Cov.: 33 AF XY: 0.00000289 AC XY: 2AN XY: 691752
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1633 of the SMARCA4 protein (p.Arg1633Gln). 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: 537831). 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 | Jul 03, 2023 | - - |
Intellectual disability, autosomal dominant 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2022 | 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; Also known as p.R1601Q; This variant is associated with the following publications: (PMID: 30111351, 30809794) - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at