rs199805770
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014140.4(SMARCAL1):āc.72A>Gā(p.Arg24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,224 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00053 ( 0 hom., cov: 33)
Exomes š: 0.0011 ( 38 hom. )
Consequence
SMARCAL1
NM_014140.4 synonymous
NM_014140.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.08
Genes affected
SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 2-216414776-A-G is Benign according to our data. Variant chr2-216414776-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 334289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-216414776-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=3.08 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000532 (81/152334) while in subpopulation SAS AF= 0.0162 (78/4828). AF 95% confidence interval is 0.0133. There are 0 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 38 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCAL1 | NM_014140.4 | c.72A>G | p.Arg24= | synonymous_variant | 3/18 | ENST00000357276.9 | |
SMARCAL1 | NM_001127207.2 | c.72A>G | p.Arg24= | synonymous_variant | 3/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCAL1 | ENST00000357276.9 | c.72A>G | p.Arg24= | synonymous_variant | 3/18 | 2 | NM_014140.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000532 AC: 81AN: 152216Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00225 AC: 566AN: 251380Hom.: 17 AF XY: 0.00327 AC XY: 444AN XY: 135902
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GnomAD4 exome AF: 0.00112 AC: 1635AN: 1461890Hom.: 38 Cov.: 32 AF XY: 0.00169 AC XY: 1230AN XY: 727246
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GnomAD4 genome ? AF: 0.000532 AC: 81AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Schimke immuno-osseous dysplasia Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 06, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Kidney disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 01, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at