12-123323733-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001167856.3(SBNO1):c.2072A>G(p.Asn691Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,612,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
SBNO1
NM_001167856.3 missense
NM_001167856.3 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.25
Genes affected
SBNO1 (HGNC:22973): (strawberry notch homolog 1) Predicted to enable chromatin DNA binding activity and histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SBNO1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.060230702).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SBNO1 | NM_001167856.3 | c.2072A>G | p.Asn691Ser | missense_variant | 16/32 | ENST00000602398.3 | |
SBNO1 | NM_018183.5 | c.2069A>G | p.Asn690Ser | missense_variant | 16/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBNO1 | ENST00000602398.3 | c.2072A>G | p.Asn691Ser | missense_variant | 16/32 | 5 | NM_001167856.3 | P4 | |
SBNO1 | ENST00000420886.6 | c.2072A>G | p.Asn691Ser | missense_variant | 15/31 | 1 | P4 | ||
SBNO1 | ENST00000267176.8 | c.2069A>G | p.Asn690Ser | missense_variant | 16/32 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460702Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726690
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 29, 2024 | The c.2072A>G (p.N691S) alteration is located in exon 15 (coding exon 15) of the SBNO1 gene. This alteration results from a A to G substitution at nucleotide position 2072, causing the asparagine (N) at amino acid position 691 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of phosphorylation at N691 (P = 0.0135);.;Gain of phosphorylation at N691 (P = 0.0135);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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