GeneBe

rs755853314

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016038.4(SBDS):​c.666G>T​(p.Glu222Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E222Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SBDS
NM_016038.4 missense

Scores

9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

Publications

0 publications found
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]
SBDS Gene-Disease associations (from GenCC):
  • Shwachman-Diamond syndrome
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Shwachman-Diamond syndrome 1
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23334923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016038.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SBDS
NM_016038.4
MANE Select
c.666G>Tp.Glu222Asp
missense
Exon 5 of 5NP_057122.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SBDS
ENST00000246868.7
TSL:1 MANE Select
c.666G>Tp.Glu222Asp
missense
Exon 5 of 5ENSP00000246868.2Q9Y3A5
SBDS
ENST00000697897.1
c.666G>Tp.Glu222Asp
missense
Exon 6 of 6ENSP00000513469.1Q9Y3A5
SBDS
ENST00000890817.1
c.666G>Tp.Glu222Asp
missense
Exon 6 of 6ENSP00000560876.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.86
D
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.23
T
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Benign
0.99
L
PhyloP100
1.6
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.77
N
REVEL
Uncertain
0.30
Sift
Benign
0.32
T
Sift4G
Benign
0.40
T
Polyphen
0.0030
B
Vest4
0.13
MutPred
0.65
Loss of methylation at K225 (P = 0.0908)
MVP
0.85
MPC
0.40
ClinPred
0.43
T
GERP RS
3.2
Varity_R
0.36
gMVP
0.44
Mutation Taster
=42/58
disease causing

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

Other links and lift over

dbSNP: rs755853314; hg19: chr7-66453445; API