rs774391397
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001387283.1(SMARCA4):c.4614C>A(p.Asp1538Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D1538D) has been classified as Likely benign.
Frequency
Consequence
NM_001387283.1 missense
Scores
Clinical Significance
Conservation
Publications
- Coffin-Siris syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
- intellectual disability, autosomal dominant 16Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- rhabdoid tumor predisposition syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
- uterine corpus sarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- familial rhabdoid tumorInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hereditary nonpolyposis colon cancerInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.4614C>A | p.Asp1538Glu | missense_variant | Exon 32 of 36 | ENST00000646693.2 | NP_001374212.1 | |
SMARCA4 | NM_003072.5 | c.4518C>A | p.Asp1506Glu | missense_variant | Exon 31 of 35 | ENST00000344626.10 | NP_003063.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.4614C>A | p.Asp1538Glu | missense_variant | Exon 32 of 36 | NM_001387283.1 | ENSP00000495368.1 | |||
SMARCA4 | ENST00000344626.10 | c.4518C>A | p.Asp1506Glu | missense_variant | Exon 31 of 35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
SMARCA4 | ENST00000643549.1 | c.4524C>A | p.Asp1508Glu | missense_variant | Exon 31 of 35 | ENSP00000493975.1 | ||||
SMARCA4 | ENST00000541122.6 | c.4428C>A | p.Asp1476Glu | missense_variant | Exon 31 of 35 | 5 | ENSP00000445036.2 | |||
SMARCA4 | ENST00000643296.1 | c.4428C>A | p.Asp1476Glu | missense_variant | Exon 30 of 34 | ENSP00000496635.1 | ||||
SMARCA4 | ENST00000644737.1 | c.4428C>A | p.Asp1476Glu | missense_variant | Exon 30 of 34 | ENSP00000495548.1 | ||||
SMARCA4 | ENST00000589677.5 | c.4425C>A | p.Asp1475Glu | missense_variant | Exon 31 of 35 | 5 | ENSP00000464778.1 | |||
SMARCA4 | ENST00000643995.1 | c.3939C>A | p.Asp1313Glu | missense_variant | Exon 28 of 32 | ENSP00000496004.1 | ||||
SMARCA4 | ENST00000644963.1 | c.3168C>A | p.Asp1056Glu | missense_variant | Exon 24 of 28 | ENSP00000495599.1 | ||||
SMARCA4 | ENST00000644065.1 | c.3150C>A | p.Asp1050Glu | missense_variant | Exon 23 of 27 | ENSP00000493615.1 | ||||
SMARCA4 | ENST00000642350.1 | c.3012C>A | p.Asp1004Glu | missense_variant | Exon 23 of 27 | ENSP00000495355.1 | ||||
SMARCA4 | ENST00000643857.1 | c.2880C>A | p.Asp960Glu | missense_variant | Exon 22 of 25 | ENSP00000494159.1 | ||||
SMARCA4 | ENST00000538456.4 | c.684C>A | p.Asp228Glu | missense_variant | Exon 5 of 8 | 3 | ENSP00000495197.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.D1538E variant (also known as c.4614C>A), located in coding exon 31 of the SMARCA4 gene, results from a C to A substitution at nucleotide position 4614. The aspartic acid at codon 1538 is replaced by glutamic acid, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.D1538E remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at