Variant 19-1108530-G-A 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_014963.3(SBNO2):c.3791C>T(p.Pro1264Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000886 in 1,219,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

SBNO2
NM_014963.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

SBNO2 (HGNC:29158): (strawberry notch homolog 2) Predicted to enable chromatin DNA binding activity and histone binding activity. Involved in several processes, including cellular response to interleukin-6; macrophage activation involved in immune response; and negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SBNO2 links:

SBNO2 (HGNC:):

SBNO2 links:

Genome browser will be placed here

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=0.25831625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO2	NM_014963.3 linkuse as main transcript	c.3791C>T	p.Pro1264Leu	missense_variant	32/32	ENST00000361757.8	NP_055778.2	Q9Y2G9-1
SBNO2	NM_001100122.2 linkuse as main transcript	c.3620C>T	p.Pro1207Leu	missense_variant	29/29		NP_001093592.1	Q9Y2G9-3
SBNO2	XM_047438466.1 linkuse as main transcript	c.2594C>T	p.Pro865Leu	missense_variant	29/29		XP_047294422.1
SBNO2	XM_011527804.4 linkuse as main transcript	c.*121C>T		3_prime_UTR_variant	32/32		XP_011526106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SBNO2	ENST00000361757.8 linkuse as main transcript	c.3791C>T	p.Pro1264Leu	missense_variant	32/32	1	NM_014963.3	ENSP00000354733.2	Q9Y2G9-1
SBNO2	ENST00000587024.5 linkuse as main transcript	c.3761C>T	p.Pro1254Leu	missense_variant	32/32	2		ENSP00000468520.1	K7ES28
SBNO2	ENST00000438103.6 linkuse as main transcript	c.3620C>T	p.Pro1207Leu	missense_variant	29/29	2		ENSP00000400762.1	Q9Y2G9-3
SBNO2	ENST00000587673.5 linkuse as main transcript	n.*35C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000801

AC:

AN:

149852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000898

AC:

AN:

1069584

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

510302

show subpopulations

Gnomad4 AFR exome

AF:

0.0000488

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00361

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000231

Gnomad4 OTH exome

AF:

0.0000243

GnomAD4 genome

AF:

0.0000800

AC:

AN:

149960

Hom.:

Cov.:

AF XY:

0.0000956

AC XY:

AN XY:

73202

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000583

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

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 12, 2024

The c.3791C>T (p.P1264L) alteration is located in exon 32 (coding exon 31) of the SBNO2 gene. This alteration results from a C to T substitution at nucleotide position 3791, causing the proline (P) at amino acid position 1264 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;.;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.046

FATHMM_MKL

Benign

0.35

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.20

Sift

Benign

0.062

T;T;.

Sift4G

Benign

0.50

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.12

MutPred

0.24

Loss of catalytic residue at P1263 (P = 0.016);.;.;

MVP

0.46

MPC

1.3

ClinPred

0.81

GERP RS

2.6

Varity_R

0.072

gMVP

0.28

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

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