rs754147208
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014140.4(SMARCAL1):āc.565A>Gā(p.Lys189Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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 (ā ). Synonymous variant affecting the same amino acid position (i.e. K189K) has been classified as Likely benign.
Frequency
Consequence
NM_014140.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCAL1 | NM_014140.4 | c.565A>G | p.Lys189Glu | missense_variant | 3/18 | ENST00000357276.9 | |
SMARCAL1 | NM_001127207.2 | c.565A>G | p.Lys189Glu | missense_variant | 3/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCAL1 | ENST00000357276.9 | c.565A>G | p.Lys189Glu | missense_variant | 3/18 | 2 | NM_014140.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Schimke immuno-osseous dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces lysine with glutamic acid at codon 189 of the SMARCAL1 protein (p.Lys189Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs754147208, ExAC 0.003%). 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 glutamic acid 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