12-123320738-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SBNO1
• BP4: Computational evidence support a benign effect (MetaRNN=0.07164508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3	c.2452T>A	p.Ser818Thr	missense_variant	18/32	ENST00000602398.3
SBNO1	NM_018183.5	c.2449T>A	p.Ser817Thr	missense_variant	18/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3	c.2452T>A	p.Ser818Thr	missense_variant	18/32	5	NM_001167856.3	P4
SBNO1	ENST00000420886.6	c.2452T>A	p.Ser818Thr	missense_variant	17/31	1		P4
SBNO1	ENST00000267176.8	c.2449T>A	p.Ser817Thr	missense_variant	18/32	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460058 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726276

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	19
Dann	Benign	0.85
DEOGEN2	Benign	0.0073	T;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T;T;.
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N;.;N
MutationTaster	Benign	0.97	D;D
PrimateAI	Uncertain	0.67	T
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	T
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.

Other links and lift over

hg19: chr12-123805285;