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GeneBe

21-33546246-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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.36
Variant links:
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.36 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 272 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SONNM_138927.4 linkuse as main transcriptc.111A>G p.Thr37= synonymous_variant 2/12 ENST00000356577.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SONENST00000356577.10 linkuse as main transcriptc.111A>G p.Thr37= synonymous_variant 2/121 NM_138927.4 P3P18583-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00179
AC:
272
AN:
152194
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00632
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000375
AC:
94
AN:
250732
Hom.:
0
AF XY:
0.000273
AC XY:
37
AN XY:
135562
show subpopulations
Gnomad AFR exome
AF:
0.00542
Gnomad AMR exome
AF:
0.000175
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000162
AC:
237
AN:
1461136
Hom.:
1
Cov.:
30
AF XY:
0.000133
AC XY:
97
AN XY:
726894
show subpopulations
Gnomad4 AFR exome
AF:
0.00616
Gnomad4 AMR exome
AF:
0.000202
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.000315
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00178
AC:
271
AN:
152312
Hom.:
2
Cov.:
33
AF XY:
0.00160
AC XY:
119
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00628
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000850
Hom.:
0
Bravo
AF:
0.00196
Asia WGS
AF:
0.000289
AC:
1
AN:
3476

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 submitterclinical testingInvitaeDec 30, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
12
Dann
Benign
0.73
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76600419; hg19: chr21-34918552; API