chr7-66995294-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_016038.4(SBDS):c.124G>A(p.Gly42Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SBDS
NM_016038.4 missense
NM_016038.4 missense
Scores
5
3
1
Clinical Significance
Conservation
PhyloP100: 4.62
Publications
0 publications found
Genes affected
SBDS (HGNC:19440): (SBDS ribosome maturation factor) This gene encodes a highly conserved protein that plays an essential role in ribosome biogenesis. The encoded protein interacts with elongation factor-like GTPase 1 to disassociate eukaryotic initiation factor 6 from the late cytoplasmic pre-60S ribosomal subunit allowing assembly of the 80S subunit. Mutations within this gene are associated with the autosomal recessive disorder Shwachman-Bodian-Diamond syndrome. This gene has a closely linked pseudogene that is distally located. [provided by RefSeq, Jan 2017]
TYW1 (HGNC:25598): (tRNA-yW synthesizing protein 1 homolog) Wybutosine (yW) is a hypermodified guanosine found in phenylalanine tRNA adjacent to the anticodon that stabilizes codon-anticodon interactions in the ribosome. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PM1
In a chain Ribosome maturation protein SBDS (size 248) in uniprot entity SBDS_HUMAN there are 12 pathogenic changes around while only 1 benign (92%) in NM_016038.4
PM2
Very rare variant in population databases, with high coverage;
PP3
REVEL computational evidence supports a deleterious effect, 0.709
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SBDS | NM_016038.4 | c.124G>A | p.Gly42Ser | missense_variant | Exon 1 of 5 | ENST00000246868.7 | NP_057122.2 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152256
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461442Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727024 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461442
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727024
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
1
AN:
86236
European-Finnish (FIN)
AF:
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
AC:
0
AN:
5498
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111950
Other (OTH)
AF:
AC:
0
AN:
60338
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74398 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152256
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74398
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41466
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5202
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68044
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Mar 29, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The p.G42S variant (also known as c.124G>A), located in coding exon 1 of the SBDS gene, results from a G to A substitution at nucleotide position 124. The glycine at codon 42 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
PhyloP100
ClinPred
D
GERP RS
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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