Variant 12-123296029-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001167856.3(SBNO1):c.4061G>A(p.Cys1354Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SBNO1
NM_001167856.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO1	NM_001167856.3 linkuse as main transcript	c.4061G>A	p.Cys1354Tyr	missense_variant	32/32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5 linkuse as main transcript	c.4058G>A	p.Cys1353Tyr	missense_variant	32/32		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.4061G>A	p.Cys1354Tyr	missense_variant	32/32	5	NM_001167856.3	ENSP00000473665.1	A3KN83-1
SBNO1	ENST00000420886.6 linkuse as main transcript	c.4061G>A	p.Cys1354Tyr	missense_variant	31/31	1		ENSP00000387361.2	A3KN83-1
SBNO1	ENST00000267176.8 linkuse as main transcript	c.4058G>A	p.Cys1353Tyr	missense_variant	32/32	5		ENSP00000267176.4	A3KN83-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461264

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726982

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 25, 2024

The c.4061G>A (p.C1354Y) alteration is located in exon 31 (coding exon 31) of the SBNO1 gene. This alteration results from a G to A substitution at nucleotide position 4061, causing the cysteine (C) at amino acid position 1354 to be replaced by a tyrosine (Y). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

0.90

L;.;L

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-7.5

D;D;.

REVEL

Pathogenic

0.82

Sift

Benign

0.067

T;T;.

Sift4G

Benign

0.15

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.92

MutPred

0.85

Loss of catalytic residue at S1356 (P = 0.0863);.;Loss of catalytic residue at S1356 (P = 0.0863);

MVP

0.63

MPC

2.2

ClinPred

1.0

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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