7-66995354-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_016038.4(SBDS):​c.64C>T​(p.Arg22Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SBDS
NM_016038.4 missense

Scores

11
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40
Variant links:
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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a chain Ribosome maturation protein SBDS (size 248) in uniprot entity SBDS_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_016038.4
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SBDSNM_016038.4 linkc.64C>T p.Arg22Cys missense_variant 1/5 ENST00000246868.7 NP_057122.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SBDSENST00000246868.7 linkc.64C>T p.Arg22Cys missense_variant 1/51 NM_016038.4 ENSP00000246868.2 Q9Y3A5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 28, 2024The p.R22C variant (also known as c.64C>T), located in coding exon 1 of the SBDS gene, results from a C to T substitution at nucleotide position 64. The arginine at codon 22 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.85
D;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Pathogenic
0.65
D
MetaRNN
Uncertain
0.72
D;D
MetaSVM
Pathogenic
0.83
D
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-5.2
D;.
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.99
D;.
Vest4
0.39
MutPred
0.55
Gain of catalytic residue at M20 (P = 0.0149);Gain of catalytic residue at M20 (P = 0.0149);
MVP
0.96
MPC
1.4
ClinPred
1.0
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.83
gMVP
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-66460341; API