chr21-33546246-A-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_138927.4(SON):c.111A>G(p.Thr37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,613,448 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0018 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
SON
NM_138927.4 synonymous
NM_138927.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
SON (HGNC:11183): (SON DNA and RNA binding protein) This gene encodes a protein that contains multiple simple repeats. The encoded protein binds RNA and promotes pre-mRNA splicing, particularly of transcripts with poor splice sites. The protein also recognizes a specific DNA sequence found in the human hepatitis B virus (HBV) and represses HBV core promoter activity. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 21-33546246-A-G is Benign according to our data. Variant chr21-33546246-A-G is described in ClinVar as [Benign]. Clinvar id is 720940.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.36 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00178 (271/152312) while in subpopulation AFR AF= 0.00628 (261/41552). AF 95% confidence interval is 0.00566. There are 2 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 272 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SON | NM_138927.4 | c.111A>G | p.Thr37= | synonymous_variant | 2/12 | ENST00000356577.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SON | ENST00000356577.10 | c.111A>G | p.Thr37= | synonymous_variant | 2/12 | 1 | NM_138927.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00179 AC: 272AN: 152194Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000375 AC: 94AN: 250732Hom.: 0 AF XY: 0.000273 AC XY: 37AN XY: 135562
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GnomAD4 exome AF: 0.000162 AC: 237AN: 1461136Hom.: 1 Cov.: 30 AF XY: 0.000133 AC XY: 97AN XY: 726894
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at