Variant chr12-123320738-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001167856.3(SBNO1):c.2452T>A(p.Ser818Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,058 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SBNO1
NM_001167856.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

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]

SBNO1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07164508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO1	NM_001167856.3 linkuse as main transcript	c.2452T>A	p.Ser818Thr	missense_variant	18/32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5 linkuse as main transcript	c.2449T>A	p.Ser817Thr	missense_variant	18/32		NP_060653.3	A3KN83-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SBNO1	ENST00000602398.3 linkuse as main transcript	c.2452T>A	p.Ser818Thr	missense_variant	18/32	5	NM_001167856.3	ENSP00000473665.1	A3KN83-1
SBNO1	ENST00000420886.6 linkuse as main transcript	c.2452T>A	p.Ser818Thr	missense_variant	17/31	1		ENSP00000387361.2	A3KN83-1
SBNO1	ENST00000267176.8 linkuse as main transcript	c.2449T>A	p.Ser817Thr	missense_variant	18/32	5		ENSP00000267176.4	A3KN83-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460058

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726276

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 09, 2022

The c.2452T>A (p.S818T) alteration is located in exon 17 (coding exon 17) of the SBNO1 gene. This alteration results from a T to A substitution at nucleotide position 2452, causing the serine (S) at amino acid position 818 to be replaced by a threonine (T). 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

0.065

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0073

T;.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

T;T;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.35

N;.;N

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.43

N;N;.

REVEL

Benign

0.076

Sift

Benign

0.32

T;T;.

Sift4G

Benign

0.62

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.19

MutPred

0.13

Loss of phosphorylation at S818 (P = 0.0379);.;Loss of phosphorylation at S818 (P = 0.0379);

MVP

0.068

MPC

0.62

ClinPred

0.42

GERP RS

5.7

Varity_R

0.069

gMVP

0.31

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over