12-123309546-A-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001167856.3(SBNO1):​c.3480T>G​(p.Asp1160Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

SBNO1
NM_001167856.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.564

Publications

2 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.046381474).
BS2
High AC in GnomAdExome4 at 51 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SBNO1NM_001167856.3 linkc.3480T>G p.Asp1160Glu missense_variant Exon 27 of 32 ENST00000602398.3 NP_001161328.1
SBNO1NM_018183.5 linkc.3477T>G p.Asp1159Glu missense_variant Exon 27 of 32 NP_060653.3 A3KN83-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SBNO1ENST00000602398.3 linkc.3480T>G p.Asp1160Glu missense_variant Exon 27 of 32 5 NM_001167856.3 ENSP00000473665.1 A3KN83-1
SBNO1ENST00000420886.6 linkc.3480T>G p.Asp1160Glu missense_variant Exon 26 of 31 1 ENSP00000387361.2 A3KN83-1
SBNO1ENST00000267176.8 linkc.3477T>G p.Asp1159Glu missense_variant Exon 27 of 32 5 ENSP00000267176.4 A3KN83-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152258
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000279
AC:
7
AN:
251298
AF XY:
0.0000294
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1461696
Hom.:
0
Cov.:
32
AF XY:
0.0000289
AC XY:
21
AN XY:
727160
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.000574
AC:
15
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39682
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53394
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000279
AC:
31
AN:
1111876
Other (OTH)
AF:
0.0000828
AC:
5
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152258
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74382
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41472
American (AMR)
AF:
0.00
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.000576
AC:
2
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5204
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68050
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.563
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000503
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 17, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.3480T>G (p.D1160E) alteration is located in exon 26 (coding exon 26) of the SBNO1 gene. This alteration results from a T to G substitution at nucleotide position 3480, causing the aspartic acid (D) at amino acid position 1160 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
13
DANN
Benign
0.73
DEOGEN2
Benign
0.0082
T;.;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.70
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.89
D;D;.
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.046
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.55
N;.;N
PhyloP100
0.56
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
1.2
N;N;.
REVEL
Benign
0.14
Sift
Benign
0.81
T;T;.
Sift4G
Benign
0.81
T;T;T
Polyphen
0.0050
B;B;B
Vest4
0.24
MutPred
0.20
Gain of helix (P = 0.0696);.;Gain of helix (P = 0.0696);
MVP
0.18
MPC
0.63
ClinPred
0.062
T
GERP RS
-0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.026
gMVP
0.40
Mutation Taster
=91/9
polymorphism

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: rs147709194; hg19: chr12-123794093; API