21-33559643-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4BP6_ModerateBP7BS2
The NM_138927.4(SON):c.6525C>T(p.Phe2175Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
SON
NM_138927.4 synonymous
NM_138927.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.08
Publications
0 publications found
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]
DONSON (HGNC:2993): (DNA replication fork stabilization factor DONSON) This gene lies downstream of the SON gene and spans 10 kb on chromosome 21. The function of this gene is unknown. [provided by RefSeq, Jul 2008]
DONSON Gene-Disease associations (from GenCC):
- microcephaly, short stature, and limb abnormalitiesInheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -8 ACMG points.
BP4
Computational evidence support a benign effect (REVEL=0.272).
BP6
Variant 21-33559643-C-T is Benign according to our data. Variant chr21-33559643-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3023193.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.08 with no splicing effect.
BS2
High AC in GnomAdExome4 at 10 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_138927.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SON | MANE Select | c.6525C>T | p.Phe2175Phe | synonymous | Exon 6 of 12 | NP_620305.3 | P18583-1 | ||
| SON | c.6525C>T | p.Phe2175Phe | synonymous | Exon 6 of 7 | NP_115571.3 | P18583-3 | |||
| SON | c.609C>T | p.Phe203Phe | synonymous | Exon 5 of 11 | NP_001278341.1 | J3QSZ5 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SON | TSL:1 MANE Select | c.6525C>T | p.Phe2175Phe | synonymous | Exon 6 of 12 | ENSP00000348984.4 | P18583-1 | ||
| SON | TSL:1 | c.6525C>T | p.Phe2175Phe | synonymous | Exon 6 of 7 | ENSP00000300278.2 | P18583-3 | ||
| SON | TSL:1 | c.609C>T | p.Phe203Phe | synonymous | Exon 5 of 11 | ENSP00000371111.2 | J3QSZ5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461720Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727166 show subpopulations
GnomAD4 exome
AF:
AC:
10
AN:
1461720
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
727166
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39686
South Asian (SAS)
AF:
AC:
0
AN:
86238
European-Finnish (FIN)
AF:
AC:
0
AN:
53390
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1111936
Other (OTH)
AF:
AC:
1
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.430
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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