Variant 12-123320586-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_001167856.3(SBNO1):c.2513A>G(p.Asn838Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,422 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 1 hom. )

Consequence

SBNO1
NM_001167856.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, SBNO1

BP4

Computational evidence support a benign effect (MetaRNN=0.025636941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3 linkuse as main transcript	c.2513A>G	p.Asn838Ser	missense_variant	19/32	ENST00000602398.3
SBNO1	NM_018183.5 linkuse as main transcript	c.2510A>G	p.Asn837Ser	missense_variant	19/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3 linkuse as main transcript	c.2513A>G	p.Asn838Ser	missense_variant	19/32	5	NM_001167856.3	P4	A3KN83-1
SBNO1	ENST00000420886.6 linkuse as main transcript	c.2513A>G	p.Asn838Ser	missense_variant	18/31	1		P4	A3KN83-1
SBNO1	ENST00000267176.8 linkuse as main transcript	c.2510A>G	p.Asn837Ser	missense_variant	19/32	5		A1	A3KN83-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250350

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461206

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

Aug 14, 2023

The c.2513A>G (p.N838S) alteration is located in exon 18 (coding exon 18) of the SBNO1 gene. This alteration results from a A to G substitution at nucleotide position 2513, causing the asparagine (N) at amino acid position 838 to be replaced by a serine (S). 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

0.057

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.73

Cadd

Benign

Dann

Benign

0.19

DEOGEN2

Benign

0.0063

T;.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

T;T;.

M_CAP

Benign

0.0022

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.020

N;N;.

REVEL

Benign

0.045

Sift

Benign

0.49

T;T;.

Sift4G

Benign

0.87

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.21

MutPred

0.17

Gain of phosphorylation at N838 (P = 0.0293);.;Gain of phosphorylation at N838 (P = 0.0293);

MVP

0.068

MPC

0.54

ClinPred

0.021

GERP RS

-1.7

Varity_R

0.019

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over