rs763670564
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014140.4(SMARCAL1):c.2735C>T(p.Ser912Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251350Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135822
GnomAD4 exome AF: 0.000167 AC: 244AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.000166 AC XY: 121AN XY: 727246
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74314
ClinVar
Submissions by phenotype
Schimke immuno-osseous dysplasia Uncertain:3
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 912 of the SMARCAL1 protein (p.Ser912Leu). This variant is present in population databases (rs763670564, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 532004). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SMARCAL1 protein function with a negative predictive value of 80%. 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. -
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Inborn genetic diseases Uncertain:1
The c.2735C>T (p.S912L) alteration is located in exon 18 (coding exon 16) of the SMARCAL1 gene. This alteration results from a C to T substitution at nucleotide position 2735, causing the serine (S) at amino acid position 912 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at