rs1312214950
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014140.4(SMARCAL1):c.922A>G(p.Ser308Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_014140.4 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 |
---|---|---|---|---|---|---|---|
SMARCAL1 | NM_014140.4 | c.922A>G | p.Ser308Gly | missense_variant | 5/18 | ENST00000357276.9 | |
SMARCAL1 | NM_001127207.2 | c.922A>G | p.Ser308Gly | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCAL1 | ENST00000357276.9 | c.922A>G | p.Ser308Gly | missense_variant | 5/18 | 2 | NM_014140.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251374Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135866
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Schimke immuno-osseous dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | This sequence change replaces serine with glycine at codon 308 of the SMARCAL1 protein (p.Ser308Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at