rs765073845
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001387283.1(SMARCA4):c.2611G>A(p.Ala871Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,457,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A871A) has been classified as Likely benign.
Frequency
Consequence
NM_001387283.1 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 | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.2611G>A | p.Ala871Thr | missense_variant | 18/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.2611G>A | p.Ala871Thr | missense_variant | 18/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.2611G>A | p.Ala871Thr | missense_variant | 18/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.2611G>A | p.Ala871Thr | missense_variant | 18/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249566Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135070
GnomAD4 exome AF: 0.00000480 AC: 7AN: 1457928Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 4AN XY: 725406
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 871 of the SMARCA4 protein (p.Ala871Thr). 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: 537824). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at